Dosimetric analysis of patients receiving volumetric-modulated arc palliative radiotherapy to the thoracic spine: A comparison with conventional mono-isocentric parallel opposed pair treatment.

PURPOSE: Volumetric modulated arc therapy (VMAT) has allowed for dose escalation and a decrease in radiation-induced toxicities for a variety of treatment sites, including spinal metastases. This article will compare the dosimetric impacts on normal lung tissue in patients treated with both VMAT and conventional treatment to the thoracic spine and determine if any significant difference exists among patient reported Edmonton Symptom Assessment System (ESAS) scores. METHODS: This retrospective quality assurance study identified 288 patients who received palliative radiotherapy to the thoracic spine using VMAT or conventional planning techniques with various palliative dose fractionation schemes. V5 lung dose levels, treated planning target volume (PTV) cord length, patient-reported ESAS scores at the time of radiation oncology consultation, 3 months' post-treatment, and 6 months' post-treatment were analyzed. All symptoms on the ESAS survey were investigated, but shortness of breath (SOB) scores were the main focus of this study. Date of death for each patient was also included for analysis. RESULTS: Patients treated with a VMAT technique had significantly higher V5 lung dose levels compared to those treated conventionally (right lung: p = 1.67e-14; left lung: p = 1.33e-6). Despite this, no significant differences were observed for SOB scores at all time points between groups and conventionally treated patients reported significantly worse pain, tiredness, depression, and wellbeing scores. A moderate correlation was observed between PTV length and nausea, SOB, appetite, and drowsiness scores in the VMAT group. Treatment technique was not found to have a significant impact on patient lifespan. CONCLUSIONS: Despite higher V5 lung dose levels associated with a VMAT technique, no significant differences were found in patient-reported ESAS scores compared to patients treated with conventional techniques. This demonstrates that palliation of thoracic spinal metastases is feasible and safe using a VMAT technique.

Palliation of Vertebral Metastases with Radiotherapy: Exploration of Volumetric-Modulated Arc Therapy From Development to Implementation in Routine Clinical Practice.

The development of volumetric-modulated arc therapy (VMAT) in radiation therapy has allowed for improved dose escalation and a decrease in radiation-induced toxicities for patients. This article will describe a single centre's experience in development and implementation of VMAT for palliation of vertebral metastases. A retrospective planning analysis of 10 cases identified that utilization of VMAT decreases overall planning time with a statistically significant improvement in target coverage when compared with the current conventional technique. PTV Dmax (P = .02), PTV V9519Gy (95%) (P = .01), dose conformation (P = 1.8e-004), and the homogeneity index (P = .019) were all superior for VMAT plans with an average PTV length of 22.46 cm. Another benefit of VMAT utilization is a significant decrease in treatment delivery time, which reduced treatment times from 9.95 minutes to 2.98 minutes. Immobilization was also carefully considered, and rotational errors were measured and fell within institutional tolerances when VMAT was delivered using simple immobilization devices. Clinical implementation of this technique, utilizing a highly conformal target volume to decrease radiation-induced toxicities and minimizing the length of time patients are required to maintain their treatment positions, aims to improve the palliative radiotherapy experience for patients with painful spinal metastases.

Impact of pretreatment tumor growth rate on outcome of early-stage lung cancer treated with stereotactic body radiation therapy.

PURPOSE: To determine the influence of pretreatment tumor growth rate on outcomes in patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: A review was conducted on 160 patients with T1-T2N0M0 NSCLC treated with SBRT at single institution. The patient's demographic and clinical data, time interval (t) between diagnostic and planning computed tomography (CT), vital status, disease status, and cause of death were extracted from a prospectively kept database. Differences in gross tumor volume between diagnostic CT (GTV1) and planning CT (GTV2) were recorded, and growth rate was calculated by use of specific growth rate (SGR). Kaplan-Meier curves were constructed for overall survival (OS). Differences between groups were compared with a log-rank test. Multivariate analyses were performed by use of the Cox proportional hazard model with SGR and other relevant clinical factors. Cumulative incidence was calculated for local, regional, and distant failures by use of the competing risk approach and was compared with Gray's test. RESULTS: The median time interval between diagnostic and planning CT was 82 days. The patients were divided into 2 groups, and the median SGR was used as a cut-off. The median survival times were 38.6 and 27.7 months for the low and high SGR groups, respectively (P=.03). Eastern Cooperative Oncology Group performance status (P=.01), sex (P=.04), SGR (P=.03), and GTV2 (P=.002) were predictive for OS in multivariable Cox regression analysis and, except sex, were similarly predictive for failure-free survival (FFS). The 3-year cumulative incidences of regional failure were 19.2% and 6.0% for the high and low SGR groups, respectively (P=.047). CONCLUSION: High SGR was correlated with both poorer OS and FFS in patients with early-stage NSCLC treated with SBRT. If validated, this measurement may be useful in identifying patients most likely to benefit from adjuvant therapy after SBRT.

The impact of tumor size on outcomes after stereotactic body radiation therapy for medically inoperable early-stage non-small cell lung cancer.

PURPOSE: Stereotactic body radiation therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC) offers excellent control rates. Most published series deal mainly with small (usually <4 cm), peripheral, solitary tumors. Larger tumors are associated with poorer outcomes (ie, lower control rates, higher toxicity) when treated with conventional RT. It is unclear whether SBRT is sufficiently potent to control these larger tumors. We therefore evaluated and examined the influence of tumor size on treatment outcomes after SBRT. METHODS AND MATERIALS: Between October 2004 and October 2010, 185 medically inoperable patients with early (T1-T2N0M0) NSCLC were treated on a prospective research ethics board-approved single-institution protocol. Prescription doses were risk-adapted based on tumor size and location. Follow-up included prospective assessment of toxicity (as per Common Terminology Criteria for Adverse Events, version 3.0) and serial computed tomography scans. Patterns of failure, toxicity, and survival outcomes were calculated using Kaplan-Meier method, and the significance of tumor size (diameter, volume) with respect to patient, treatment, and tumor factors was tested. RESULTS: Median follow-up was 15.2 months. Tumor size was not associated with local failure but was associated with regional failure (P=.011) and distant failure (P=.021). Poorer overall survival (P=.001), disease-free survival (P=.001), and cause-specific survival (P=.005) were also significantly associated with tumor size (with tumor volume more significant than diameter). Gross tumor volume and planning target volume were significantly associated with grade 2 or worse radiation pneumonitis. However, overall rates of grade ≥3 pneumonitis were low and not significantly affected by tumor or target size. CONCLUSIONS: Currently employed stereotactic body radiation therapy dose regimens can provide safe effective local therapy even for larger solitary NSCLC tumors (up to 5.7 cm in tumor diameter or 100 cm(3) in tumor volume) but are associated with more nonlocal failures as well as poorer survival. These observations suggest these patients may benefit from more extensive staging or consideration of adjuvant therapy.

Predictors of radiotherapy induced bone injury (RIBI) after stereotactic lung radiotherapy.

BACKGROUND: The purpose of this study was to identify clinical and dosimetric factors associated with radiotherapy induced bone injury (RIBI) following stereotactic lung radiotherapy. METHODS: Inoperable patients with early stage non-small cell lung cancer, treated with SBRT, who received 54 or 60 Gy in 3 fractions, and had a minimum of 6 months follow up were reviewed. Archived treatment plans were retrieved, ribs delineated individually and treatment plans re-computed using heterogeneity correction. Clinical and dosimetric factors were evaluated for their association with rib fracture using logistic regression analysis; a dose-event curve and nomogram were created. RESULTS: 46 consecutive patients treated between Oct 2004 and Dec 2008 with median follow-up 25 months (m) (range 6 - 51 m) were eligible. 41 fractured ribs were detected in 17 patients; median time to fracture was 21 m (range 7 - 40 m). The mean maximum point dose in non-fractured ribs (n=1054) was 10.5 Gy ± 10.2 Gy, this was higher in fractured ribs (n=41) 48.5 Gy ± 24.3 Gy (p<0.0001). On univariate analysis, age, dose to 0.5 cc of the ribs (D0.5), and the volume of the rib receiving at least 25 Gy (V25), were significantly associated with RIBI. As D0.5 and V25 were cross-correlated (Spearman correlation coefficient: 0.57, p<0.001), we selected D0.5 as a representative dose parameter. On multivariate analysis, age (odds ratio: 1.121, 95% CI: 1.04 - 1.21, p=0.003), female gender (odds ratio: 4.43, 95% CI: 1.68 - 11.68, p=0.003), and rib D0.5 (odds ratio: 1.0009, 95% CI: 1.0007 - 1.001, p<0.0001) were significantly associated with rib fracture.Using D0.5, a dose-event curve was constructed estimating risk of fracture from dose at the median follow up of 25 months after treatment. In our cohort, a 50% risk of rib fracture was associated with a D0.5 of 60 Gy. CONCLUSIONS: Dosimetric and clinical factors contribute to risk of RIBI and both should be included when modeling risk of toxicity. A nomogram is presented using D0.5, age, and female gender to estimate risk of RIBI following SBRT. This requires validation.

Stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC): is FDG-PET a predictor of outcome?

BACKGROUND AND PURPOSE: Distant metastases are the dominant mode of failure after stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC). The primary study objective was to evaluate if the maximum standardized uptake value (SUV(max)) on pre-treatment FDG-PET/CT predicted clinical outcomes. Secondary objectives were to correlate 3-month post-SBRT SUV(max) and change in SUV(max) with outcomes. MATERIALS AND METHODS: Consecutive patients with medically inoperable early-stage NSCLC and an FDG-PET/CT scan before (n=82) and 3 months after (n=62) SBRT. RESULTS: Median follow up was 2 years. On univariate analysis baseline SUV(max) predicted for distant failure (p=0.0096), relapse free survival (RFS) (p=0.037) and local failure (p=0.044). On multivariate analysis baseline SUV(max) predicted for RFS (p=0.037). Baseline SUV(max) of above 5 was the most statistically significant cut off point for predicting distant failure (p=0.0002). Baseline SUV(max) ≥4.75 (median) was correlated with a higher risk of distant failure (p=0.012) and poorer RFS (p=0.04). Patients with a post-SBRT SUV(max) ≥2 and a reduction of <2.55 had a significantly higher rate of distant failure. CONCLUSIONS: Pre-SBRT SUV(max) on FDG-PET/CT correlated most strongly with distant failure. A cut off of ≥5 was the most significant. Post-SBRT SUV(max) ≥2 and a reduction of <2.55 were associated with a higher risk of distant failure.

Stereotactic body radiotherapy for medically inoperable lung cancer: prospective, single-center study of 108 consecutive patients.

PURPOSE: To present the results of stereotactic body radiotherapy (SBRT) for medically inoperable patients with Stage I non-small-cell lung cancer (NSCLC) and contrast outcomes in patients with and without a pathologic diagnosis. METHODS AND MATERIALS: Between December 2004 and October 2008, 108 patients (114 tumors) underwent treatment according to the prospective research ethics board-approved SBRT protocols at our cancer center. Of the 108 patients, 88 (81.5%) had undergone pretreatment whole-body [18F]-fluorodeoxyglucose positron emission tomography/computed tomography. A pathologic diagnosis was unavailable for 33 (28.9%) of the 114 lesions. The SBRT schedules included 48 Gy in 4 fractions or 54-60 Gy in 3 fractions for peripheral lesions and 50-60 Gy in 8-10 fractions for central lesions. Toxicity and radiologic response were assessed at the 3-6-month follow-up visits using conventional criteria. RESULTS: The mean tumor diameter was 2.4-cm (range, 0.9-5.7). The median follow-up was 19.1 months (range, 1-55.7). The estimated local control rate at 1 and 4 years was 92% (95% confidence interval [CI], 86-97%) and 89% (95% CI, 81-96%). The cause-specific survival rate at 1 and 4 years was 92% (95% CI, 87-98%) and 77% (95% CI, 64-89%), respectively. No statistically significant difference was found in the local, regional, and distant control between patients with and without pathologically confirmed NSCLC. The most common acute toxicity was Grade 1 or 2 fatigue (53 of 108 patients). No toxicities of Grade 4 or greater were identified. CONCLUSIONS: Lung SBRT for early-stage NSCLC resulted in excellent local control and cause-specific survival with minimal toxicity. The disease-specific outcomes were comparable for patients with and without a pathologic diagnosis. SBRT can be considered an option for selected patients with proven or presumed early-stage NSCLC.

Effect of immobilization and performance status on intrafraction motion for stereotactic lung radiotherapy: analysis of 133 patients.

PURPOSE: To assess intrafractional geometric accuracy of lung stereotactic body radiation therapy (SBRT) patients treated with volumetric image guidance. METHODS AND MATERIALS: Treatment setup accuracy was analyzed in 133 SBRT patients treated via research ethics board-approved protocols. For each fraction, a localization cone-beam computed tomography (CBCT) scan was acquired for soft-tissue registration to the internal target volume, followed by a couch adjustment for positional discrepancies greater than 3 mm, verified with a second CBCT scan. CBCT scans were also performed at intrafraction and end fraction. Patient positioning data from 2047 CBCT scans were recorded to determine systematic (Σ) and random (σ) uncertainties, as well as planning target volume margins. Data were further stratified and analyzed by immobilization method (evacuated cushion [n=75], evacuated cushion plus abdominal compression [n=33], or chest board [n=25]) and by patients' Eastern Cooperative Oncology Group performance status (PS): 0 (n=31), 1 (n=70), or 2 (n=32). RESULTS: Using CBCT internal target volume was matched within ±3 mm in 16% of all fractions at localization, 89% at verification, 72% during treatment, and 69% after treatment. Planning target volume margins required to encompass residual setup errors after couch corrections (verification CBCT scans) were 4 mm, and they increased to 5 mm with target intrafraction motion (post-treatment CBCT scans). Small differences (<1 mm) in the cranial-caudal direction of target position were observed between the immobilization cohorts in the localization, verification, intrafraction, and post-treatment CBCT scans (p<0.01). Positional drift varied according to patient PS, with the PS 1 and 2 cohorts drifting out of position by mid treatment more than the PS 0 cohort in the cranial-caudal direction (p=0.04). CONCLUSIONS: Image guidance ensures high geometric accuracy for lung SBRT irrespective of immobilization method or PS. A 5-mm setup margin suffices to address intrafraction motion. This setup margin may be further reduced by strategies such as frequent image guidance or volumetric arc therapy to correct or limit intrafraction motion.

Treatment planning study to determine potential benefit of intensity-modulated radiotherapy versus conformal radiotherapy for unresectable hepatic malignancies.

PURPOSE: To compare intensity-modulated radiotherapy (IMRT) with conformal RT (CRT) for hypofractionated isotoxicity liver RT and explore dose escalation using IMRT for the same/improved nominal risk of liver toxicity in a treatment planning study. METHODS AND MATERIALS: A total of 26 CRT plans were evaluated. Prescription doses (24-54 Gy within six fractions) were individualized on the basis of the effective liver volume irradiated maintaining < or =5% risk of radiation-induced liver disease. The dose constraints included bowel (0.5 cm(3)) and stomach (0.5 cm(3)) to < or =30 Gy, spinal cord to < or =25 Gy, and planning target volume (PTV) to < or =140% of the prescribed dose. Two groups were evaluated: (1) PTV overlapping or directly adjacent to serial functioning normal tissues (n = 14), and (2) the liver as the dose-limiting normal tissue (n = 12). IMRT plans using direct machine parameter optimization maintained the CRT plan beam arrangements, an estimated radiation-induced liver disease risk of 5%, and underwent dose escalation, if all normal tissue constraints were maintained. RESULTS: IMRT improved PTV coverage in 19 of 26 plans (73%). Dose escalation was feasible in 9 cases by an average of 3.8 Gy (range, 0.6-13.2) in six fractions. Three of seven plans without improved PTV coverage had small gross tumor volumes (< or =105 cm(3)) already receiving 54 Gy, the maximal prescription dose allowed. In the remaining cases, the PTV range was 9.6-689 cm(3); two had overlapped organs at risk; and one had four targets. IMRT did not improve these plans owing to poor target coverage (n = 2) and nonliver (n = 2) dose limits. CONCLUSION: Direct machine parameter optimization IMRT improved PTV coverage while maintaining normal tissue tolerances in most CRT liver plans. Dose escalation was possible in a minority of patients.

Upper abdominal malignancies: intensity-modulated radiation therapy.

Local control and survival of most upper abdominal malignancies are poor. Challenges associated with the safe delivery of tumoricidal doses of radiation therapy to these malignancies include organ motion due to breathing, gastrointestinal filling and peristalsis, and the presence of many normal tissues with a low tolerance to radiation. Intensity-modulated radiation therapy (IMRT) can facilitate normal tissue sparing and dose escalation to these tumors, which has the potential to reduce toxicity and improve local control. Planning studies have demonstrated the potential for dose escalation with IMRT. However, degradation of upper abdominal IMRT plans in the presence of organ motion has also been demonstrated. Thus, organ motion reduction and image guidance strategies should be implemented in conjunction with IMRT. Clinical experience with dose-escalated IMRT is limited, and IMRT should continue to be studied in clinical trials before it is routinely used for upper abdominal malignancies.