Variability in spine radiosurgery treatment planning - results of an international multi-institutional study.

BACKGROUND: The aim of this study was to quantify the variability in spinal radiosurgery (SRS) planning practices between five international institutions, all member of the Elekta Spine Radiosurgery Research Consortium. METHODS: Four institutions provided one representative patient case each consisting of the medical history, CT and MR imaging. A step-wise planning approach was used where, after each planning step a consensus was generated that formed the basis for the next planning step. This allowed independent analysis of all planning steps of CT-MR image registration, GTV definition, CTV definition, PTV definition and SRS treatment planning. In addition, each institution generated one additional SRS plan for each case based on intra-institutional image registration and contouring, independent of consensus results. RESULTS: Averaged over the four cases, image registration variability ranged between translational 1.1 mm and 2.4 mm and rotational 1.1° and 2.0° in all three directions. GTV delineation variability was 1.5 mm in axial and 1.6 mm in longitudinal direction averaged for the four cases. CTV delineation variability was 0.8 mm in axial and 1.2 mm in longitudinal direction. CTV-to-PTV margins ranged between 0 mm and 2 mm according to institutional protocol. Delineation variability was 1 mm in axial directions for the spinal cord. Average PTV coverage for a single fraction18 Gy prescription was 87 ± 5 %; Dmin to the PTV was 7.5 ± 1.8 Gy averaged over all cases and institutions. Average Dmax to the PRV_SC (spinal cord + 1 mm) was 10.5 ± 1.6 Gy and the average Paddick conformity index was 0.69 ± 0.06. CONCLUSIONS: Results of this study reflect the variability in current practice of spine radiosurgery in large and highly experienced academic centers. Despite close methodical agreement in the daily workflow, clinically significant variability in all steps of the treatment planning process was demonstrated. This may translate into differences in patient clinical outcome and highlights the need for consensus and established delineation and planning criteria.

Toxicity after central versus peripheral lung stereotactic body radiation therapy: a propensity score matched-pair analysis.

PURPOSE: To compare toxicity after stereotactic body radiation therapy (SBRT) for "central" tumors-within 2 cm of the proximal bronchial tree or with planning tumor volume (PTV) touching mediastinum-versus noncentral ("peripheral") lung tumors. METHODS AND MATERIALS: From November 2005 to January 2011, 229 tumors (110 central, 119 peripheral; T1-3N0M0 non-small-cell lung cancer and limited lung metastases) in 196 consecutive patients followed prospectively at a single institution received moderate-dose SBRT (48-60 Gy in 4-5 fractions [biologic effective dose=100-132 Gy, α/ß=10]) using 4-dimensional planning, online image-guided radiation therapy, and institutional dose constraints. Clinical adverse events (AEs) were graded prospectively at clinical and radiographic follow-up using Common Terminology Criteria for Adverse Events version 3.0. Pulmonary function test (PFT) decline was graded as 2 (25%-49.9% decline), 3 (50.0%-74.9% decline), or 4 (≥75.0% decline). Central/peripheral location was assessed retrospectively on planning CT scans. Groups were compared after propensity score matching. Characteristics were compared with χ(2) and 2-tailed t tests, adverse events with χ(2) test-for-trend, and cumulative incidence using competing risks analysis (Gray's test). RESULTS: With 79 central and 79 peripheral tumors matched, no differences in AEs were observed after 17 months median follow-up. Two-year cumulative incidences of grade ≥2 pain, musculoskeletal, pulmonary, and skin AEs were 14%, 5%, 6%, and 10% (central) versus 19%, 10%, 10%, and 3% (peripheral), respectively (P=.31, .38, .70, and .09). Grade ≥2 cardiovascular, gastrointestinal, and central nervous system AEs were rare (<1%). Two-year incidences of grade ≥2 clinical AEs (28% vs 25%, P=.79), grade ≥2 PFT decline (36% vs 34%, P=.94), grade ≥3 clinical AEs (3% vs 7%, P=.48), and grade ≥3 PFT decline (0 vs 10%, P=.11) were similar for central versus peripheral tumors, respectively. Pooled 2-year incidences of grades 4 and 5 AEs were <1% and 0%, respectively, in both the prematched and matched groups. CONCLUSION: Moderate-dose SBRT with these techniques yields a similarly safe toxicity profile for both central and peripheral lung tumors.

Trigeminal neuralgia pain relief after gamma knife stereotactic radiosurgery.

OBJECTIVES: To report outcomes of patients with medical and/or surgical refractory trigeminal neuralgia (TN) treated with gamma knife stereotactic radiosurgery (GK SRS). METHODS: One hundred and forty-nine patients with 152 cases of TN treated with GK SRS were analyzed. All patients, except one, received a dose of 40Gy to the 50% isodose volume. The Barrow Neurological Institute (BNI) pain intensity score was used to grade pain. Actuarial rates of pain relief were calculated. Multiple factors were analyzed for association with pain relief. RESULTS: The median follow up was 27 months (4-71 months). Overall 92% of cases achieved a BNI score I-III after GK SRS. Of those who had pain relief after GK SRS, 32% developed pain recurrence defined as a BNI score of IV or V. The actuarial rate of freedom from pain recurrence (BNI scores I-III) of all treated cases at 1, 2 and 3-years was 76%, 69% and 60%, respectively. On univariate analysis age ≥70 was predictive of better pain relief (p=0.046). Type of pain, prior surgery, multiple sclerosis, number of isocenters, treated nerve length, volume and thickness and distance from the root entry zone to the isocenter were not significant for maintaining a BNI score of I-III. Those who achieved a BNI score of I or II were more likely to maintain pain relief compared to those who only achieved a BNI score of III (93% vs 38% at three years, p<0.01). The rate of pain relief of twenty-seven patients who underwent repeat GK SRS was 70% and 62% at 1 and 2 years, respectively. Toxicity after first GK SRS was minimal with 25% of cases experiencing only new or worsening post-treatment numbness. CONCLUSION: GK SRS provides acceptable pain relief with limited morbidity in patients with medical and/or surgical refractory TN.

Tumor volume as a predictor of survival and local control in patients with brain metastases treated with Gamma Knife surgery.

OBJECT: The aim of this study was to examine tumor volume as a prognostic factor for patients with brain metastases treated with Gamma Knife surgery (GKS). METHODS: Two hundred fifty patients with 1-14 brain metastases who had initially undergone GKS alone at a single institution were retrospectively reviewed. Patients who received upfront whole brain radiation therapy were excluded. Survival times were estimated using the Kaplan-Meier method. Univariate and multivariate analyses using Cox proportional hazard regression models were used to determine if various prognostic factors could predict overall survival, distant brain failure, and local control. RESULTS: Median overall survival was 7.1 months and the 1-year local control rate was 91.5%. Median time to distant brain failure was 8.0 months. On univariate analysis an increasing total tumor volume was significantly associated with worse survival (p = 0.031) whereas the number of brain metastases, analyzed as a continuous variable, was not (p = 0.082). After adjusting for age, Karnofsky Performance Scale score, and extracranial disease on multivariate analysis, total tumor volume was found to be a better predictor of overall survival (p = 0.046) than number of brain metastases analyzed as a continuous variable (p = 0.098). A total tumor volume cutoff value of ≥ 2 cm(3) (p = 0.008) was a stronger predictor of overall survival than the number of brain metastases (p = 0.098). Larger tumor volume and extracranial disease, but not the number of brain metastases, were predictive of distant brain failure on multivariate analysis. Local tumor control at 1 year was 97% for lesions < 2 cm(3) compared with 75% for lesions ≥ 2 cm(3) (p < 0.001). CONCLUSIONS: After adjusting for other factors, a total brain metastasis volume was a strong and independent predictor for overall survival, distant brain failure, and local control, even when considering the number of metastases.

A collaborative analysis of stereotactic lung radiotherapy outcomes for early-stage non-small-cell lung cancer using daily online cone-beam computed tomography image-guided radiotherapy.

INTRODUCTION: We report lung stereotactic-body radiotherapy (SBRT) outcomes for a large pooled cohort treated using daily online cone-beam computed tomography. METHODS: Five hundred and five stage I-IIB (T1-3N0M0) non-small-cell lung cancer (NSCLC) cases underwent SBRT using cone-beam computed tomography image guidance at five international institutions from 1998 to 2010. Median age was 74 years (range, 42-92) whereas median forced expiratory volume in 1 second/diffusing lung capacity for carbon monoxide were 1.4 liter (65%) and 10.8 ml/min/mmHg (53%). Of the 505 cases, 64% were biopsy proven and 87% medically inoperable. Staging was: IA 63%, IB 33%, IIA 2%, and recurrent 1%. Median max tumor dimension was 2.6 cm (range, 0.9-8.5). Median heterogeneously calculated volumetric prescription dose (PD) was 54 Gy (range, 20-64 Gy) in three fractions (range, 1-15) over 8 days (range, 1-27). Median biologically equivalent PD biological equivalent doses (BED10) was 132 Gy (range, 60-180). RESULTS: With a median follow-up of 1.6 years (range, 0.1-7.3), the 2-year Kaplan-Meier local control (LC), regional control, and distant metastasis (DM) rates were 94%, 89%, and 20%, respectively, whereas cause-specific and overall survival were 87% and 60% (78% operable, 58% inoperable, p = 0.01), respectively. Stage, gross-tumor volume size (≥ 2.7 cm) and PD(BED10) predicted local relapse (LR) and DM. LR was 15% for BED10 less than 105 Gy versus 4% for BED10 of 105 Gy or more (p < 0.001); DM was 31% versus 18% for BED10 less than 105 versus 105 Gy or more (p = 0.01). On multivariate analysis, PD(BED10) and elapsed days during radiotherapy predicted LR; gross-tumor volume size predicted DM. Grade 2 or higher pneumonitis, rib fracture, myositis, and dermatitis were 7%, 3%, 1%, and 2%, respectively. CONCLUSIONS: In the largest early-stage NSCLC SBRT data set to date, a high rate of local control was achieved, which was correlated with a PD(BED10) of 105 Gy or more. Failures were primarily distant, severe toxicities were rare, and overall survival was encouraging in operable patients.

Differentiation between intra-axial metastatic tumor progression and radiation injury following fractionated radiation therapy or stereotactic radiosurgery using MR spectroscopy, perfusion MR imaging or volume progression modeling.

OBJECTIVE: To determine the accuracy of magnetic resonance spectroscopy (MRS), perfusion MR imaging (MRP), or volume modeling in distinguishing tumor progression from radiation injury following radiotherapy for brain metastasis. METHODS: Twenty-six patients with 33 intra-axial metastatic lesions who underwent MRS (n=41) with or without MRP (n=32) after cranial irradiation were retrospectively studied. The final diagnosis was based on histopathology (n=4) or magnetic resonance imaging (MRI) follow-up with clinical correlation (n=29). Cho/Cr (choline/creatinine), Cho/NAA (choline/N-acetylaspartate), Cho/nCho (choline/contralateral normal brain choline) ratios were retrospectively calculated for the multi-voxel MRS. Relative cerebral blood volume (rCBV), relative peak height (rPH) and percentage of signal-intensity recovery (PSR) were also retrospectively derived for the MRPs. Tumor volumes were determined using manual segmentation method and analyzed using different volume progression modeling. Different ratios or models were tested and plotted on the receiver operating characteristic curve (ROC), with their performances quantified as area under the ROC curve (AUC). MRI follow-up time was calculated from the date of initial radiotherapy until the last MRI or the last MRI before surgical diagnosis. RESULTS: Median MRI follow-up was 16 months (range: 2-33). Thirty percent of lesions (n=10) were determined to be radiation injury; 70% (n=23) were determined to be tumor progression. For the MRS, Cho/nCho had the best performance (AUC of 0.612), and Cho/nCho >1.2 had 33% sensitivity and 100% specificity in predicting tumor progression. For the MRP, rCBV had the best performance (AUC of 0.802), and rCBV >2 had 56% sensitivity and 100% specificity. The best volume model was percent increase (AUC of 0.891); 65% tumor volume increase had 100% sensitivity and 80% specificity. CONCLUSION: Cho/nCho of MRS, rCBV of MRP, and percent increase of MRI volume modeling provide the best discrimination of intra-axial metastatic tumor progression from radiation injury for their respective modalities. Cho/nCho and rCBV appear to have high specificities but low sensitivities. In contrast, percent volume increase of 65% can be a highly sensitive and moderately specific predictor for tumor progression after radiotherapy. Future incorporation of 65% volume increase as a pretest selection criterion may compensate for the low sensitivities of MRS and MRP.

Longitudinal assessment of quality of life and audiometric test outcomes in vestibular schwannoma patients treated with gamma knife surgery.

OBJECTIVE: To prospectively assess the quality of life (QOL) and hearing acuity in vestibular schwannoma (VS) patients after gamma knife surgery (GKS). PATIENTS: Fifty-nine VS patients. INTERVENTION: GKS. MAIN OUTCOME MEASURES: Prospective follow-up algorithm included 36-item Short Form Health Survey (SF-36), Hearing Handicap Inventory (HHI), Dizziness Handicap Inventory (DHI), Tinnitus Handicap Inventory (THI), pure-tone average, and speech discrimination hearing scores (Gardner-Robertson and American Academy of Otolaryngology), performed before and after GKS at 1-, 3-, 6-, 12-, and 18-month posttreatment intervals. RESULTS: From December 2006 to November 2008, 59 VS patients were treated with a median follow-up of 15 months. At baseline, mean scores for SF-36, HHI, DHI, and THI were 73, 37, 17, and 23, respectively. Median baseline Gardner-Robertson and American Academy of Otolaryngology hearing acuity scores were 2 and B, respectively. No significant decline in SF-36 health survey was noted after GKS. Mean SF-36 score at baseline was 73, compared with a range of 70 to 77 at predetermined posttreatment intervals. Similarly, no significant changes in DHI, HHI, and THI were noted. Approximately 47% of patients with baseline serviceable hearing maintained serviceable hearing at 12 months. Significant acute and chronic worsening in hearing acuity were noted at 1 and 18 months, respectively. No correlative decline in QOL was noted as assessed by SF-36 or HHI. CONCLUSION: No significant decline in global QOL occurred after GKS with relatively short follow-up and approximately 50% survey completion. When discussing therapy options with VS patients, anticipated treatment-related QOL outcomes should be considered.

Accelerated partial breast irradiation for pure ductal carcinoma in situ.

PURPOSE: To report outcomes for ductal carcinoma in situ (DCIS) treated with breast-conserving therapy using accelerated partial breast irradiation (APBI). METHODS AND MATERIALS: From March 2001 to February 2009, 53 patients with Stage 0 breast cancer were treated with breast conserving surgery and adjuvant APBI. Median age was 62 years. All patients underwent excision with margins negative by ≥1 mm before adjuvant radiotherapy (RT). A total of 39 MammoSite brachytherapy (MS) patients and 14 three-dimensional conformal external beam RT (3DCRT) patients were treated to the lumpectomy bed alone with 34 Gy and 38.5 Gy, respectively. Of the DCIS cases, 94% were mammographically detected. All patients with calcifications had either specimen radiography or postsurgical mammography confirmation of clearance. Median tumor size was 6 mm, and median margin distance was 5 mm. There were no statistically significant differences according to APBI method for race/ethnicity, tumor detection method, tumor grade, estrogen receptor (ER) status, or use of tamoxifen (p = NS). Recurrence and survival were calculated using the Kaplan-Meier method. Cosmesis was scored by the Harvard criteria. RESULTS: With a median follow-up of 3.6 years (range, 0.4-6.3 years), the overall and cause-specific survival rates were 98% and 100%, respectively. Three-year actuarial ipsilateral breast tumor recurrence was 2%. One failure was observed at the resection bed 11 months post-RT. No other elsewhere breast failures, regional recurrences, or distant metastases were noted. Cosmesis was excellent or good in 92.4% of cases, with no statistically significant differences according to the APBI method (92.3% with MammoSite and 92.8% with 3DCRT; p = 0.649). CONCLUSIONS: APBI as part of breast-conserving therapy for pure DCIS was associated with excellent local control and survival rates, with the vast majority of patients having good to excellent cosmesis. This finding supports the recent analysis by the American Society of Breast Surgeons on a subset of DCIS patients treated efficaciously with APBI.

Rapid disease progression with delay in treatment of non-small-cell lung cancer.

PURPOSE: To assess rate of disease progression from diagnosis to initiation of treatment for Stage I-IIIB non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Forty patients with NSCLC underwent at least two sets of computed tomography (CT) and 18-fluorodeoxyglucose positron emission tomography (PET) scans at various time intervals before treatment. Progression was defined as development of any new lymph node involvement, site of disease, or stage change. RESULTS: Median time interval between first and second CT scans was 13.4 weeks, and between first and second PET scans was 9.0 weeks. Median initial primary maximum tumor dimension (MTD) was 3.5 cm (0.6-8.5 cm) with a median standardized uptake value (SUV) of 13.0 (1.7-38.5). The median MTD increased by a median of 1.0 cm (mean, 1.6 cm) between scans for a median relative MTD increase of 35% (mean, 59%). Nineteen patients (48%) progressed between scans. Rate of any progression was 13%, 31%, and 46% at 4, 8, and 16 weeks, respectively. Upstaging occurred in 3%, 13%, and 21% at these intervals. Distant metastasis became evident in 3%, 13%, and 13% after 4, 8, and 16 weeks, respectively. T and N stage were associated with progression, whereas histology, grade, sex, age, and maximum SUV were not. At 3 years, overall survival for Stage III patients with vs. without progression was 18% vs. 67%, p = 0.05. CONCLUSIONS: With NSCLC, treatment delay can lead to disease progression. Diagnosis, staging, and treatment initiation should be expedited. After 4-8 weeks of delay, complete restaging should be strongly considered.