To determine treatment accuracy and margins for stereotactic lung radiotherapy with and without cone-beam CT (CBCT) image guidance.
Acquired for the study were 308 CBCT of 24 patients with solitary ...peripheral lung tumors treated with stereotactic radiotherapy. Patients were immobilized in a stereotactic body frame (SBF) or alpha-cradle and treated with image guidance using daily CBCT. Four (T1) or five (T2/metastatic) 12-Gy fractions were prescribed to the planning target volume (PTV) edge. The PTV margin was >or=5 mm depending on a pretreatment estimate of tumor excursion. Initial daily setup was according to SBF coordinates or tattoos for alpha-cradle cases. A CBCT was performed and registered to the planning CT using soft tissue registration of the target. The initial setup error/precorrection position, was recorded for the superior-inferior, anterior-posterior, and medial-lateral directions. The couch was adjusted to correct the tumor positional error. A second CBCT verified tumor position after correction. Patients were treated in the corrected position after the residual errors were <or=2 mm. A final CBCT after treatment assessed intrafraction tumor displacement.
The precorrection systematic (Sigma) and random errors (sigma) for the population ranged from 2-3 mm for SBF and 2-6 mm for alpha-cradle patients; postcorrection errors ranged from 0.4-1.0 mm. Calculated population margins were 9 to 13 mm (SBF) and 10-14 mm (cradle) precorrection, 1-2 mm (SBF), and 2-3 mm (cradle) postcorrection, and 2-4 mm (SBF) and 2-5 mm (cradle) posttreatment.
Setup for stereotactic lung radiotherapy using a SBF or alpha-cradle alone is suboptimal. CBCT image guidance significantly improves target positioning and substantially reduces required target margins and normal tissue irradiation.
PURPOSE To compare outcomes between lung stereotactic radiotherapy (SBRT) and wedge resection for stage I non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS One hundred twenty-four patients ...with T1-2N0 NSCLC underwent wedge resection (n = 69) or image-guided lung SBRT (n = 58) from February 2003 through August 2008. All were ineligible for anatomic lobectomy; of those receiving SBRT, 95% were medically inoperable, with 5% refusing surgery. Mean forced expiratory volume in 1 second and diffusing capacity of lung for carbon monoxide were 1.39 L and 12.0 mL/min/mmHg for wedge versus 1.31 L and 10.14 mL/min/mmHg for SBRT (P = not significant). Mean Charlson comorbidity index and median age were 3 and 74 years for wedge versus 4 and 78 years for SBRT (P < .01, P = .04). SBRT was volumetrically prescribed as 48 (T1) or 60 (T2) Gy in four to five fractions. Results Median potential follow-up is 2.5 years. At 30 months, no significant differences were identified in regional recurrence (RR), locoregional recurrence (LRR), distant metastasis (DM), or freedom from any failure (FFF) between the two groups (P > .16). SBRT reduced the risk of local recurrence (LR), 4% versus 20% for wedge (P = .07). Overall survival (OS) was higher with wedge but cause-specific survival (CSS) was identical. Results excluding synchronous primaries, nonbiopsied tumors, or pathologic T4 disease (wedge satellite lesion) showed reduced LR (5% v 24%, P = .05), RR (0% v 18%, P = .07), and LRR (5% v 29%, P = .03) with SBRT. There were no differences in DM, FFF, or CSS, but OS was higher with wedge. CONCLUSION Both lung SBRT and wedge resection are reasonable treatment options for stage I NSCLC patients ineligible for anatomic lobectomy. SBRT reduced LR, RR, and LRR. In this nonrandomized population of patients selected for surgery versus SBRT (medically inoperable) at physician discretion, OS was higher in surgical patients. SBRT and surgery, however, had identical CSS.
We report lung stereotactic-body radiotherapy (SBRT) outcomes for a large pooled cohort treated using daily online cone-beam computed tomography.
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).
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.
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.
An increasing serum prostate-specific antigen (PSA) level is the initial sign of recurrent prostate cancer among patients treated with radical prostatectomy. Salvage radiation therapy (SRT) may ...eradicate locally recurrent cancer, but studies to distinguish local from systemic recurrence lack adequate sensitivity and specificity. We developed a nomogram to predict the probability of cancer control at 6 years after SRT for PSA-defined recurrence.
Using multivariable Cox regression analysis, we constructed a model to predict the probability of disease progression after SRT in a multi-institutional cohort of 1,540 patients.
The 6-year progression-free probability was 32% (95% CI, 28% to 35%) overall. Forty-eight percent (95% CI, 40% to 56%) of patients treated with SRT alone at PSA levels of 0.50 ng/mL or lower were disease free at 6 years, including 41% (95% CI, 31% to 51%) who also had a PSA doubling time of 10 months or less or poorly differentiated (Gleason grade 8 to 10) cancer. Significant variables in the model were PSA level before SRT (P < .001), prostatectomy Gleason grade (P < .001), PSA doubling time (P < .001), surgical margins (P < .001), androgen-deprivation therapy before or during SRT (P < .001), and lymph node metastasis (P = .019). The resultant nomogram was internally validated and had a concordance index of 0.69.
Nearly half of patients with recurrent prostate cancer after radical prostatectomy have a long-term PSA response to SRT when treatment is administered at the earliest sign of recurrence. The nomogram we developed predicts the outcome of SRT and should prove valuable for medical decision making for patients with a rising PSA level.
Recent randomized studies have suggested improvements in progression-free and overall survival with the addition of stereotactic body radiation therapy (SBRT, also known as SABR) in patients with ...oligometastatic non-small cell lung cancer. Given the novelty and complexity of incorporating SBRT in the oligometastatic setting, the multidisciplinary American Radium Society Lung Cancer Panel was assigned to create appropriate use criteria on SBRT as part of consolidative local therapy for patients with oligometastatic and oligoprogressive non-small cell lung cancer.
A review of the current literature was conducted from January 1, 2008, to December 25, 2020, using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to systematically search the PubMed database to retrieve a comprehensive set of relevant articles.
Based on representation in existing randomized trials, the panel defined the term "oligometastasis" as ≤3 metastatic deposits (not including the primary tumor) in the previously untreated setting or after first-line systemic therapy after the initial diagnosis. "Oligoprogression" also referred to ≤3 discrete areas of progression in the setting of prior or ongoing receipt of systemic therapy. In all appropriate patients, the panel strongly recommends enrollment in a clinical trial whenever available. For oligometastatic disease, administering first-line systemic therapy followed by consolidative radiation therapy (to all sites plus the primary/nodal disease) is preferred over up-front radiation therapy. Owing to a dearth of data, the panel recommended that consolidative radiation therapy be considered on a case-by-case basis for 4 to 5 sites of oligometastatic disease, driver mutation-positive oligometastatic disease without progression on up-front targeted therapy, and oligoprogressive cases.
Although SBRT/SABR appears to be both safe and effective in treating patients with limited metastatic sites of disease, many clinical circumstances require individualized management and strong multidisciplinary discussion on account of the limited existing data.
To validate the interval to biochemical failure (IBF) as a prognostic factor at the time of biochemical failure for prostate cancer mortality (PCM) following radiotherapy (RT).
From a collaborative ...data set of men with clinically localized prostate cancer treated with RT from four institutions in three countries, we identified 1,722 men with biochemical failure (BF; prostate-specific antigen nadir + 2 ng/mL). The IBF was defined as the time interval from completion of treatment to the date of BF. The primary outcome measure was discriminatory power in the form of the concordance index (c-index).
Seventeen percent of men had an IBF ≤ 18 months. Median potential follow-up beyond the time of BF was 67 months. There were 290 deaths from prostate cancer. The IBF was the most discriminating individual prognostic factor overall, with a sensitivity of IBF ≤ 18 months to predict PCM within 10 years of 48.4% (95% CI, 43.3% to 54.1%); the specificity was 86.1% (95% CI, 84.5% to 87.7%), equating to a c-index of 0.611 (95% CI, 0.578 to 0.647). The 5-year cumulative incidence of PCM for IBF more than 18 months versus IBF ≤ 18 months was 9.4% (95% CI, 7.7% to 11.5%) versus 26.3% (95% CI, 21.2% to 31.8%); corresponding 10-year estimates were 26.2% (95% CI, 21.5% to 30.8%) versus 55.9% (95% CI, 48.9% to 63.0%), respectively (P < .001 for both). IBF exhibited minimal change in performance across various follow-up durations.
IBF is the single most robust prognostic factor for PCM following RT without androgen deprivation therapy. This external validation demonstrates that patients and clinicians can use this information to make decisions about subsequent treatments.
Prolonged delivery times during daily cone-beam computed tomography (CBCT)-guided lung stereotactic body radiotherapy (SBRT) introduce concerns regarding intrafraction variation (IFV) of the mean ...target position (MTP). The purpose of this study was to evaluate the magnitude of the IFV-MTP and to assess target margins required to compensate for IFV and postonline CBCT correction residuals. Patient, treatment, and tumor characteristics were analyzed with respect to their impact on IFV-MTP.
A total of 126 patients with 140 tumors underwent 659 fractions of lung SBRT. Dose prescribed was 48 or 60 Gy in 12 Gy fractions. Translational target position correction of the MTP was performed via onboard CBCT. IFV-MTP was measured as the difference in MTP between the postcorrection CBCT and the posttreatment CBCT excluding residual error.
IFV-MTP was 0.2 ± 1.8 mm, 0.1 ± 1.9 mm, and 0.01 ± 1.5 mm in the craniocaudal, anteroposterior, and mediolateral dimensions and the IFV-MTP vector was 2.3 ± 2.1 mm. Treatment time and excursion were found to be significant predictors of IFV-MTP. An IFV-MTP vector greater than 2 and 5 mm was seen in 40.8% and 7.2% of fractions, respectively. IFV-MTP greater than 2 mm was seen in heavier patients with larger excursions and longer treatment times. Significant differences in IFV-MTP were seen between immobilization devices. The stereotactic frame immobilization device was found to be significantly less likely to have an IFV-MTP vector greater than 2 mm compared with the alpha cradle, BodyFIX, and hybrid immobilization devices.
Treatment time and respiratory excursion are significantly associated with IFV-MTP. Significant differences in IFV-MTP were found between immobilization devices. Target margins for IFV-MTP plus post-correction residuals are dependent on immobilization device with 5-mm uniform margins being acceptable for the frame immobilization device.
Rectal distension has been shown to decrease the probability of biochemical control. Adaptive image-guided radiotherapy (IGRT) corrects for target position and volume variations, reducing the risk of ...biochemical failure while yielding acceptable rates of gastrointestinal (GI)/genitourinary (GU) toxicities.
Between 1998 and 2006, 962 patients were treated with computed tomography (CT)-based offline adaptive IGRT. Patients were stratified into low (n = 400) vs. intermediate/high (n = 562) National Comprehensive Cancer Network (NCCN) risk groups. Target motion was assessed with daily CT during the first week. Electronic portal imaging device (EPID) was used to measure daily setup error. Patient-specific confidence-limited planning target volumes (cl-PTV) were then constructed, reducing the standard PTV and compensating for geometric variation of the target and setup errors. Rectal volume (RV), cross-sectional area (CSA), and rectal volume from the seminal vesicles to the inferior prostate (SVP) were assessed on the planning CT. The impact of these volumetric parameters on 5-year biochemical control (BC) and chronic Grades ≥2 and 3 GU and GI toxicity were examined.
Median follow-up was 5.5 years. Median minimum dose covering cl-PTV was 75.6 Gy. Median values for RV, CSA, and SVP were 82.8 cm(3), 5.6 cm(2), and 53.3 cm(3), respectively. The 5-year BC was 89% for the entire group: 96% for low risk and 83% for intermediate/high risk (p < 0.001). No statistically significant differences in BC were seen with stratification by RV, CSA, and SVP in quartiles. Maximum chronic Grades ≥2 and 3 GI toxicities were 21.2% and 2.9%, respectively. Respective values for GU toxicities were 15.5% and 4.3%. No differences in GI or GU toxicities were noted when patients were stratified by RV.
Incorporation of adaptive IGRT reduces the risk of geometric miss and results in excellent biochemical control that is independent of rectal volume/distension while maintaining very low rates of chronic GI toxicity.
Hypofractionated stereotactic body radiation therapy (SBRT) has emerged as an effective treatment option for early-stage non-small cell lung cancer (NSCLC). Using data collected by the Elekta Lung ...Research Group, we generated a tumor control probability (TCP) model that predicts 2-year local control after SBRT as a function of biologically effective dose (BED) and tumor size.
We formulated our TCP model as follows: TCP = e(BED10 - c ∗ L - TCD50/k) ÷ (1 + e(BED10 - c ∗ L - TCD50/k)), where BED10 is the biologically effective SBRT dose, c is a constant, L is the maximal tumor diameter, and TCD50 and k are parameters that define the shape of the TCP curve. Least-squares optimization with a bootstrap resampling approach was used to identify the values of c, TCD50, and k that provided the best fit with observed actuarial 2-year local control rates.
Data from 504 NSCLC tumors treated with a variety of SBRT schedules were available. The mean follow-up time was 18.4 months, and 26 local recurrences were observed. The optimal values for c, TCD50, and k were 10 Gy/cm, 0 Gy, and 31 Gy, respectively. Thus, size-adjusted BED (sBED) may be defined as BED minus 10 times the tumor diameter (in centimeters). Our TCP model indicates that sBED values of 44 Gy, 69 Gy, and 93 Gy provide 80%, 90%, and 95% chances of tumor control at 2 years, respectively. When patients were grouped by sBED, the model accurately characterized the relationship between sBED and actuarial 2-year local control (r=0.847, P=.008).
We have developed a TCP model that predicts 2-year local control rate after hypofractionated SBRT for early-stage NSCLC as a function of biologically effective dose and tumor diameter. Further testing of this model with additional datasets is warranted.
To systematically evaluate four different techniques of radiation therapy (RT) used to treat non–small-cell lung cancer and to determine their efficacy in meeting multiple normal-tissue constraints ...while maximizing tumor coverage and achieving dose escalation.
Treatment planning was performed for 18 patients with Stage I to IIIB inoperable non–small-cell lung cancer using four different RT techniques to treat the primary lung tumor ± the hilar/mediastinal lymph nodes: (
1) Intensity-modulated radiation therapy (IMRT), (
2) Optimized three-dimensional conformal RT (3D-CRT) using multiple beam angles, (
3) Limited 3D-CRT using only 2 to 3 beams, and (
4) Traditional RT using elective nodal irradiation (ENI) to treat the mediastinum. All patients underwent virtual simulation, including a CT scan and
18fluorodeoxyglucose positron emission tomography scan, fused to the CT to create a composite tumor volume. For IMRT and 3D-CRT, the target included the primary tumor and regional nodes either ≥1.0 cm in short-axis dimension on CT or with increased uptake on PET. For ENI, the target included the primary tumor plus the ipsilateral hilum and mediastinum from the inferior head of the clavicle to at least 5.0 cm below the carina. The goal was to deliver 70 Gy to ≥99% of the planning target volume (PTV) in 35 daily fractions (46 Gy to electively treated mediastinum) while meeting multiple normal-tissue dose constraints. Heterogeneity correction was applied to all dose calculations (maximum allowable heterogeneity within PTV 30%). Pulmonary and esophageal constraints were as follows: lung
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20 ≤25%, mean lung dose ≤15 Gy, esophagus
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50 ≤25%, mean esophageal dose ≤25 Gy. At the completion of all planning, the four techniques were contrasted for their ability to achieve the set dose constraints and deliver tumoricidal RT doses.
Requiring a minimum dose of 70 Gy within the PTV, we found that IMRT was associated with a greater degree of heterogeneity within the target and, correspondingly, higher mean doses and tumor control probabilities (TCPs), 7%–8% greater than 3D-CRT and 14%–16% greater than ENI. Comparing the treatment techniques in this manner, we found only minor differences between 3D-CRT and IMRT, but clearly greater risks of pulmonary and esophageal toxicity with ENI. The mean lung
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20 was 36% with ENI vs. 23%–25% with the three other techniques, whereas the average mean lung dose was approximately 21.5 Gy (ENI) vs. 15.5 Gy (others). Similarly, the mean esophagus
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50 was doubled with ENI, to 34% rather than 15%–18%. To account for differences in heterogeneity, we also compared the techniques giving each plan a tumor control probability equivalent to that of the optimized 3D-CRT plan delivering 70 Gy. Using this method, IMRT and 3D-CRT offered similar results in node-negative cases (mean lung and esophageal normal-tissue complication probability NTCP of approximately 10% and 2%–7%, respectively), but ENI was distinctly worse (mean NTCPs of 29% and 20%). In node-positive cases, however, IMRT reduced the lung
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20 and mean dose by approximately 15% and lung NTCP by 30%, compared to 3D-CRT. Compared to ENI, the reductions were 50% and >100%. Again, for node-positive cases, especially where the gross tumor volume was close to the esophagus, IMRT reduced the mean esophagus
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50 by 40% (vs. 3D-CRT) to 145% (vs. ENI). The esophageal NTCP was at least doubled converting from IMRT to 3D-CRT and tripled converting from IMRT to ENI. Finally, the total number of fractions for each plan was increased or decreased until all outlined normal-tissue constraints were reached/satisfied. While meeting all constraints, IMRT or 3D-CRT increased the deliverable dose in node-negative patients by >200% over ENI. In node-positive patients, IMRT increased the deliverable dose 25%–30% over 3D-CRT and 130%–140% over ENI. The use of 3D-CRT without IMRT increased the deliverable RT dose >80% over ENI. Using a limited number of 3D-CRT beams decreased the lung
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20, mean dose, and NTCP in node-positive patients.
The use of 3D-CRT, particularly with only 3 to 4 beam angles, has the ability to reduce normal-tissue toxicity, but has limited potential for dose escalation beyond the current standard in node-positive patients. IMRT is of limited additional value (compared to 3D-CRT) in node-negative cases, but is beneficial in node-positive cases and in cases with target volumes close to the esophagus. When meeting all normal-tissue constraints in node-positive patients, IMRT can deliver RT doses 25%–30% greater than 3D-CRT and 130%–140% greater than ENI. Whereas the possibility of dose escalation is severely limited with ENI, the potential for pulmonary and esophageal toxicity is clearly increased.
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