Limited utility of routine surveillance MRI following chemoradiation for advanced-stage oropharynx carcinoma.

Objectives. To determine the utility of routine surveillance MRI in detecting locoregional recurrence following definitive chemoradiation in advanced-stage oropharynx carcinoma. Methods. We identified patients with Stage III-IV oropharynx carcinoma who were treated with chemoradiation between April 2000 and September 2004 and underwent longitudinal followup care at our institution. Patient charts were retrospectively reviewed for findings on MRI surveillance imaging, clinical signs and symptoms, and recurrence. Results. Forty patients received a total of 229 surveillance MRI scans with a minimum follow-up of three years (mean of 5.6 scans per patient). Six patients experienced false-positive surveillance studies that resulted in intervention. Four patients experienced recurrent disease, two of whom had new symptoms or exam findings that preceded radiographic identification of disease. Surveillance MRI scans identified recurrent disease in two asymptomatic patients who were salvaged, one of whom remains free of disease at follow-up. The overall sensitivity and specificity of the MRI surveillance program were 50 and 83 percent, respectively. The mean charge to each patient for the surveillance program was approximately $10,000 annually. Conclusion. In oropharyngeal cancer patients who have been treated with chemoradiation, an imaging surveillance program utilizing MRI produces limited opportunity for successful salvage.

Dose gradient near target-normal structure interface for nonisocentric CyberKnife and isocentric intensity-modulated body radiotherapy for prostate cancer.

PURPOSE: The treatment planning quality between nonisocentric CyberKnife (CK) and isocentric intensity modulation treatment was studied for hypofractionated prostate body radiotherapy. In particular, the dose gradient across the target and the critical structures such as the rectum and bladder was characterized. METHODS AND MATERIALS: In the present study, patients treated with CK underwent repeat planning for nine fixed-field intensity-modulated radiotherapy (IMRT) using identical contour sets and dose-volume constraints. To calculate the dose falloff, the clinical target volume contours were expanded 30 mm anteriorly and posteriorly and 50 mm uniformly in other directions for all patients in the CK and IMRT plans. RESULTS: We found that all the plans satisfied the dose-volume constraints, with the CK plans showing significantly better conformity than the IMRT plans at a relative greater dose inhomogeneity. The rectal and bladder volumes receiving a low dose were also lower for CK than for IMRT. The average conformity index, the ratio of the prescription isodose volume and clinical target volume, was 1.18 +/- 0.08 for the CK plans vs. 1.44 +/- 0.11 for the IMRT plans. The average homogeneity index, the ratio of the maximal dose and the prescribed dose to the clinical target volume, was 1.45 +/- 0.12 for the CK plans vs. 1.28 +/- 0.06 for the IMRT plans. The average percentage of dose falloff was 2.9% +/- 0.8%/mm for CK and 3.1% +/- 1.0%/mm for IMRT in the anterior direction, 3.8% +/- 1.6%/mm for CK and 3.2% +/- 1.9%/mm for IMRT in the posterior direction, and 3.6% +/- 0.4% for CK and 3.6% +/- 0.4% for IMRT in all directions. CONCLUSION: Nonisocentric CK was as capable of producing equivalent fast dose falloff as high-number fixed-field IMRT delivery.

Equivalence in dose fall-off for isocentric and nonisocentric intracranial treatment modalities and its impact on dose fractionation schemes.

PURPOSE: To investigate whether dose fall-off characteristics would be significantly different among intracranial radiosurgery modalities and the influence of these characteristics on fractionation schemes in terms of normal tissue sparing. METHODS AND MATERIALS: An analytic model was developed to measure dose fall-off characteristics near the target independent of treatment modalities. Variations in the peripheral dose fall-off characteristics were then examined and compared for intracranial tumors treated with Gamma Knife, Cyberknife, or Novalis LINAC-based system. Equivalent uniform biologic effective dose (EUBED) for the normal brain tissue was calculated. Functional dependence of the normal brain EUBED on varying numbers of fractions (1 to 30) was studied for the three modalities. RESULTS: The derived model fitted remarkably well for all the cases (R(2) > 0.99). No statistically significant differences in the dose fall-off relationships were found between the three modalities. Based on the extent of variations in the dose fall-off curves, normal brain EUBED was found to decrease with increasing number of fractions for the targets, with alpha/beta ranging from 10 to 20. This decrease was most pronounced for hypofractionated treatments with fewer than 10 fractions. Additionally, EUBED was found to increase slightly with increasing number of fractions for targets with alpha/beta ranging from 2 to 5. CONCLUSION: Nearly identical dose fall-off characteristics were found for the Gamma Knife, Cyberknife, and Novalis systems. Based on EUBED calculations, normal brain sparing was found to favor hypofractionated treatments for fast-growing tumors with alpha/beta ranging from 10 to 20 and single fraction treatment for abnormal tissues with low alpha/beta values such as alpha/beta = 2.

Nonrandom intrafraction target motions and general strategy for correction of spine stereotactic body radiotherapy.

PURPOSE: To characterize nonrandom intrafraction target motions for spine stereotactic body radiotherapy and to develop a method of correction via image guidance. The dependence of target motions, as well as the effectiveness of the correction strategy for lesions of different locations within the spine, was analyzed. METHODS AND MATERIALS: Intrafraction target motions for 64 targets in 64 patients treated with a total of 233 fractions were analyzed. Based on the target location, the cases were divided into three groups, i.e., cervical (n = 20 patients), thoracic (n = 20 patients), or lumbar-sacrum (n = 24 patients) lesions. For each case, time-lag autocorrelation analysis was performed for each degree of freedom of motion that included both translations (x, y, and z shifts) and rotations (roll, yaw, and pitch). A general correction strategy based on periodic interventions was derived to determine the time interval required between two adjacent interventions, to overcome the patient-specific target motions. RESULTS: Nonrandom target motions were detected for 100% of cases regardless of target locations. Cervical spine targets were found to possess the highest incidence of nonrandom target motion compared with thoracic and lumbar-sacral lesions (p < 0.001). The average time needed to maintain the target motion to within 1 mm of translation or 1 degrees of rotational deviation was 5.5 min, 5.9 min, and 7.1 min for cervical, thoracic, and lumbar-sacrum locations, respectively (at 95% confidence level). CONCLUSIONS: A high incidence of nonrandom intrafraction target motions was found for spine stereotactic body radiotherapy treatments. Periodic interventions at approximately every 5 minutes or less were needed to overcome such motions.

Gamma Knife radiosurgery for brain metastases from primary breast cancer.

PURPOSE: The relative roles of stereotactic radiosurgery (SRS) vs. whole brain radiotherapy (WBRT) in the treatment of patients with brain metastases from breast cancer remain undefined. In this study, we reviewed our experience with these patients. MATERIALS AND METHODS: We retrospectively reviewed all patients treated between 1991 and 2005 with Gamma Knife SRS for brain metastases from breast cancer. The actuarial survival and freedom from progression endpoints were calculated using the Kaplan-Meier method. RESULTS: Between 1991 and 2005, 176 patients underwent SRS for brain metastases from breast cancer. The median survival time was 16.0 months for 95 newly diagnosed patients and 11.7 months for 81 patients with recurrent brain metastases. In the newly diagnosed patients, omission of upfront WBRT did not significantly affect the MST (p = .20), brain freedom from progression (p = .75), or freedom from new brain metastases (p = .83). Longer survival was associated with age <50 years, Karnofsky performance score >or=70, primary tumor control, estrogen receptor positivity, and Her2/neu overexpression. No association was found between the number of treated brain metastases and the survival time. CONCLUSION: We have described prognostic factors for breast cancer patients treated with SRS for newly diagnosed or recurrent brain metastases. Most patient subsets had a median survival time of >or=11 months. Unexpectedly, upfront WBRT did not appear to improve brain freedom from progression, and a larger number of brain metastases was not associated with a shorter survival time. Breast cancer might be distinct from other primary sites in terms of prognostic factors and the roles of WBRT and SRS for brain metastases.

Stereotactic body radiotherapy is effective salvage therapy for patients with prior radiation of spinal metastases.

PURPOSE: To provide actuarial outcomes and dosimetric data for spinal/paraspinal metastases, with and without prior radiation, treated with stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS: A total of 39 consecutive patients (60 metastases) were treated with SBRT between April 2003 and August 2006 and retrospectively reviewed. In all, 23 of 60 tumors had no previous radiation (unirradiated) and 37/60 tumors had previous irradiation (reirradiated). Of 37 reirradiated tumors, 31 were treated for "salvage" given image-based tumor progression. Local failure was defined as progression by imaging and/or clinically. RESULTS: At last follow-up, 19 patients were deceased. Median patient survival time measured was 21 months (95% CI = 8-27 months), and the 2-year survival probability was 45%. The median total dose prescribed was 24 Gy in three fractions prescribed to the 67% and 60% isodose for the unirradiated and reirradiated cohorts, respectively. The median tumor follow-up for the unirradiated and reirradiated group was 9 months (range, 1-26) and 7 months (range, 1-48) respectively. Eight of 60 tumors have progressed, and the 1- and 2-year progression-free probability (PFP) was 85% and 69%, respectively. For the salvage group the 1 year PFP was 96%. There was no significant difference in overall survival or PFP between the salvage reirradiated vs. all other tumors treated (p = 0.08 and p = 0.31, respectively). In six of eight failures the minimum distance from the tumor to the thecal sac was or=6 months follow-up and no radiation-induced myelopathy or radiculopathy has occurred. CONCLUSION: Spine SBRT has shown preliminary efficacy and safety in patients with image-based progression of previously irradiated metastases.

Surgical resection and permanent iodine-125 brachytherapy for brain metastases.

PURPOSE: To evaluate the efficacy and toxicity of surgical resection and permanent iodine-125 brachytherapy without adjuvant whole brain radiation therapy (WBRT) for brain metastases. METHODS AND MATERIALS: Forty patients were treated with permanent iodine-125 brachytherapy at the time of resection of brain metastases from 1997 to 2003. Actuarial freedom from progression (FFP) and survival were measured from the date of surgery and estimated using the Kaplan-Meier method, with censoring at last imaging for FFP endpoints. RESULTS: The median survival was 11.3 months overall, 12.0 months in 19 patients with newly diagnosed brain metastases and 7.3 months in 21 patients with recurrent brain metastases. Twenty-two patients (55%) remained free of progression of brain metastases, three failed at the resection cavity (including one with leptomeningeal dissemination), two failed with leptomeningeal spread only, and 13 failed elsewhere in the brain including two who also had leptomeningeal disease. The 1-year resection cavity FFP probabilities were 92%, 86% and 88%; and brain FFP probabilities were 29%, 43% and 37% for the newly diagnosed, recurrent and all patients, respectively. Symptomatic necrosis developed 7.4-40.0 months (median, 19.5 months) after brachytherapy in 9 patients (23%), confirmed by resection in 6 patients. CONCLUSIONS: Excellent local control was achieved using permanent iodine-125 brachytherapy for brain metastasis resection cavities, although there is a high risk of radiation necrosis over time. These data support consideration of permanent brachytherapy without adjuvant WBRT as a treatment option in patients with symptomatic or large newly diagnosed or recurrent brain metastases.

Split-volume treatment planning of multiple consecutive vertebral body metastases for cyberknife image-guided robotic radiosurgery.

Cyberknife treatment planning of multiple consecutive vertebral body metastases is challenging due to large target volumes adjacent to critical normal tissues. A split-volume treatment planning technique was developed to improve the treatment plan quality of such lesions. Treatment plans were generated for 1 to 5 consecutive thoracic vertebral bodies (CVBM) prescribing a total dose of 24 Gy in 3 fractions. The planning target volume (PTV) consisted of the entire vertebral body(ies). Treatment plans were generated considering both the de novo clinical scenario (no prior radiation), imposing a dose limit of 8 Gy to 1 cc of spinal cord, and the retreatment scenario (prior radiation) with a dose limit of 3 Gy to 1 cc of spinal cord. The split-volume planning technique was compared with the standard full-volume technique only for targets ranging from 2 to 5 CVBM in length. The primary endpoint was to obtain best PTV coverage by the 24 Gy prescription isodose line. A total of 18 treatment plans were generated (10 standard and 8 split-volume). PTV coverage by the 24-Gy isodose line worsened consistently as the number of CVBM increased for both the de novo and retreatment scenario. Split-volume planning was achieved by introducing a 0.5-cm gap, splitting the standard full-volume PTV into 2 equal length PTVs. In every case, split-volume planning resulted in improved PTV coverage by the 24-Gy isodose line ranging from 4% to 12% for the de novo scenario and, 8% to 17% for the retreatment scenario. We did not observe a significant trend for increased monitor units required, or higher doses to spinal cord or esophagus, with split-volume planning. Split-volume treatment planning significantly improves Cyberknife treatment plan quality for CVBM, as compared to the standard technique. This technique may be of particular importance in clinical situations where stringent spinal cord dose limits are required.

Intensity-modulated chemoradiation for treatment of stage III and IV oropharyngeal carcinoma: the University of California-San Francisco experience.

BACKGROUND: Treatment outcomes for stage III and IV oropharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy without prior surgical resection were reviewed. METHODS: Between April 2000 and September 2004, 71 patients underwent IMRT concurrent with chemotherapy without prior surgical resection for stage III and IV oropharyngeal carcinoma. Chemotherapy was platinum based. The gross tumor volume (GTV) received 70 Gy in 2.12 Gy per fraction. The high-risk clinical tumor volume (CTV) received 59.4 Gy in 1.80 Gy per fraction, and the low-risk CTV received 54 Gy in 1.64 Gy per fraction. RESULTS: With a median follow-up of 33 months, the 3-year local, regional, and locoregional progression-free probabilities were 94%, 94%, and 90%, respectively. The 3-year overall survival estimate was 83%. Locoregional failures occurred in the GTV in 7 patients. Acute grade 3 or 4 toxicity developed in 35 patients. A feeding gastrostomy was placed in 25 patients. Late xerostomia was grade 0 in 16 patients, grade 1 in 31 patients, and grade 2 in 24 patients at last follow-up. No patients experienced grade 3 or 4 late toxicity, except for 1 who developed osteoradionecrosis of the mandible. CONCLUSIONS: Excellent local and regional control was achieved with IMRT and concurrent chemotherapy without prior surgical resection in the treatment of stage III and IV oropharyngeal carcinoma. Significant sparing of the parotid glands and other critical normal tissues was possible using IMRT with moderate acute toxicities and minimal severe late effects.

Effect of composite sector collimation on average dose fall-off for Gamma Knife Perfexion.

OBJECT: The new capability of composite sector collimation in Gamma Knife Perfexion produces complex, nonspherical, and nonelliptical dose distributions. In this study, the authors investigated the effect of composite sector collimation on average dose fall-off compared with the previous Gamma Knife model. METHODS: A general formalism was derived to describe the peripheral dose distribution of all Gamma Knife models in the form of (V/V(0)) = (D/D(0))(gamma), where V is the volume of the peripheral isodose line with the value of D, V(0) is the reference prescription isodose volume, D(0) is the prescription dose, and gamma is the fitting parameter that determines how fast the dose falls off near the target. Based on this formula, the authors compared 40 cases involving patients treated with Gamma Knife Perfexion with 40 similar cases involving patients treated with Gamma Knife model 4C. The cases were grouped based on the use of the sector collimators in the treatment planning process. For each group as well as all cases combined, the mean gamma values were compared by means of the Student t-test for varying ranges of the peripheral dose distribution-from 100% of the prescription dose to 75, 50, and 25% of the prescription dose. RESULTS: The fit of general formula to the data was excellent for both Gamma Knife Perfexion and Gamma Knife 4C with R(2)> 0.99 for all the cases. The overall gamma values (mean +/- 2 standard deviations) were as follows: gamma = -1.74 +/- 0.47 (Model 4C) versus -1.77 +/- 0.40 (Perfexion) within 100-75% of the prescription dose; gamma = -1.57 +/- 0.26 (Model 4C) versus -1.58 +/- 0.25 (Perfexion) within 100-50% of the prescription dose; gamma = -1.47 +/- 0.18 (Model 4C) versus -1.50 +/- 0.16 (Perfexion) within 100-25% of the prescription dose. No statistical significance between the mean differences for Gamma Knife Perfexion and Model 4C was found within these ranges. The probability values were 0.65, 0.84, and 0.22, respectively. CONCLUSIONS: The use of composite sector collimators in Gamma Knife Perfexion demonstrated no statistically significant effects on the volume-averaged dose fall-off near a target periphery for typical treatment cases.

Gamma knife radiosurgery for brainstem metastases: the UCSF experience.

PURPOSE: To assess clinical and imaging outcomes in patients treated with Gamma Knife stereotactic radiosurgery (SRS) for brainstem metastases. MATERIALS AND METHODS: We reviewed all patients with brain metastases treated with SRS at the University of California, San Francisco from 1991-2005 to identify patients who had SRS to a brainstem metastasis. Survival time and freedom from progression (FFP) were calculated from date of SRS using the Kaplan-Meier method. Prognostic factors were evaluated using the log-rank test and Cox proportional hazards model. RESULTS: From 1991 through 2005, 42 consecutive patients with brainstem metastases had SRS to 44 lesions (seven midbrain, 31 pontine, and six medullary) in 42 sessions. Primary diagnoses included 14 cases of lung cancer (one small-cell), 10 melanoma, 12 breast cancer, five renal cell, and one unknown. The median age was 55 years (range, 25-79). The median survival time was 9 months after SRS. Longer survival time was associated with single metastasis, non-melanoma histology, and extracranial disease control. The median target volume was 0.26 ml (0.015-2.8 ml) and the median prescribed dose was 16.0 Gy (10.0-19.8 Gy). Brainstem lesion FFP was 90% at 6 months and 77% at 1 year. Four patients had brainstem complications following treatment. Poor brainstem outcome was associated with melanoma and renal cell histology as well as brainstem lesion volume > or =1 ml. CONCLUSIONS: In this series, SRS using a median dose of 16 Gy provided excellent local control with relatively low morbidity in patients with brainstem metastases less than 1 ml or non-melanoma, non-renal cell histology.

Effects of residual target motion for image-tracked spine radiosurgery.

A quality assurance method was developed to investigate the effects of residual target motion for hypofractionated spine radiosurgery. The residual target motion (target movement between successive image-guided corrections) was measured on-line via dual x-ray imagers for patients treated with CyberKnife (Accuray, Inc., Sunnyvale, CA), a robotic linear accelerator with intrafractional image-tracking capability. The six degree-of-freedom characteristics of the residual target motion were analyzed, the effects of such motion on patient treatment delivery were investigated by incorporating the probability distribution of the residual motion into the treatment planning dose calculations, and deviations of the doses from those originally planned were calculated. Measurements using a programmable motion phantom were also carried out and compared with the static treatment plan calculations. It was found that the residual target motions were patient specific and typically on the order of 2 mm. The measured dose distributions incorporating the residual target motion also exhibited 2.0 mm discrepancy at the prescription isodose level when compared with the static treatment plan calculations. For certain patients, residual errors introduced significant uncertainties (-1 Gy) for the dose delivered to the spinal cord, especially at the high dose levels covering a small volume of the spinal cord (e.g., 0.1 cc). In such cases, stringent cord constraints and frequent monitoring of the target position should be implemented.

Higher radiation dose with a shorter treatment duration improves outcome for locally advanced carcinoma of anal canal.

AIM: To assess whether radiation dose and duration of treatment influence local control and survival of patients with locally advanced anal cancer treated with definitive chemoradiation. METHODS: Twenty-eight consecutive patients who were treated with definitive radiation therapy for bulky anal cancers (> 5 cm in size) were reviewed. Nineteen patients had T3 lesions, 8 patients had T4 lesions, and 15 patients had lymph node involvement. The median tumor size was 7.5 cm. All but one patient received concurrent chemoradiation. The median radiation dose was 54 Gy. The median duration of treatment was 58 d. RESULTS: With a median follow-up of 2.5 years in all patients and 7.8 years in living patients, the 2-year local recurrence-free probability was 57% and overall survival rate was 67%. Neither radiation dose nor duration of treatment alone was predictive of either time to local failure or overall survival. However, longer treatment breaks can potentially mask an advantage over higher radiation doses. Therefore, we examined those patients who received >or= 54 Gy within 60 d, comparing them to the rest of the patients. Of patients who received >or= 54 Gy within 60 d, local progression-free probability was 89% versus 42% for the rest of the group (P=0.01). CONCLUSION: Local failure is a significant problem in locally advanced carcinomas of the anal canal. Higher radiation doses with limited treatment breaks may offer an increase in local control and survival.