All conventional 3D plan evaluation methods apply to SBRT plan, but three criteria are specially considered: dose conformality, dose gradient, and dose heterogeneity.

Since SBRT delivers high dose (often >5 Gy per fraction) in a small number of fractions (≤5), high-dose conformality is required to minimize the dose to the normal tissue. A frequently used conformality index is defined as the ratio of volume receiving prescription dose to the PTV. A perfect plan should have conformality index equal to 1, i.e., PTV is covered by 100 % of prescription dose and no normal tissue receives the prescription dose or above. This is not realistic. Usually the conformality index of 1.3 is achievable. The index could be larger for smaller target or irregular target. In current or recently closed RTOG protocols of lung SBRT [10], for the target with maximum dimension between 2 and 7 cm, the conformality index was required to be less than 1.2, and the plan was considered as minor deviation with index between 1.2 and 1.4 but there is no good data to suggest complications are higher with a poor conformality index. As with similar data with intracranial SRS, target volume and proximity to critical structures usually trump the effect of conformality.

A sharp dose gradient out of PTV is desirable for SBRT plans. The dose gradient can be evaluated by how much %/mm or ratio of volume receiving 50 % of prescription dose to the PTV that was used in RTOG protocols of lung SBRT [10]. Usually a sharp dose-off isotropically is preferred although this can be limited to less degrees of freedom with non-coplanar fields, but the dose gradient can be larger in one direction if close to a critical structure.

The dose heterogeneity is probably not as important as the above two parameters, although it needs attention. To increase the plan conformality index and dose gradient usually increase the dose heterogeneity. The dose hot spot should be within the PTV, and the best place is the center of the PTV.

The dose constraints to critical organs are different with what are used in the conventional therapy. So far the dose tolerance is still immature and the dose to organ at risk should be evaluated carefully according to the peer-reviewed publications or protocols.

The dose calculation heterogeneity correction is desirable for SBRT planning, especially for lung or spine SBRT. The treatment planning system (TPS) should be carefully evaluated to see if it is suitable for SBRT planning or specific site. Pencil beam algorithms have been discouraged for tumor sites surrounded by low-density tissue [59]. It has been reported that there was significant dose difference in the target periphery between pencil beam algorithm and superposition convolution algorithm for the lung SBRT [59]. Although the Monte Carlo simulation is the most accurate dose calculation algorithm, it may not be widely available for commercial TPS and take more time for dose calculation. The convolution superposition algorithm is more suitable considering the accuracy and calculation time is rather similar to Monte Carlo-generated plans.

Early in the North American experience with lung cancer, heterogeneity corrections were not used because tissue density correction dose algorithms were not widely available. In the absence of heterogeneity corrections, tumors completely surrounded by air experience a dose build-up effect due to the loss of electronic equilibrium, such that the periphery of a tumor is under-dosed, and a higher dose is required to achieve optimal cell kill [66]. Tumors that lack this air–tissue interface, such as tumors abutting the chest wall or central tumors, may have artificially high doses (“hot spot”) delivered to the PTV, due to dose being delivered through low-density air using very long path lengths. Xiao et al. [67] applied heterogeneity corrections to the original treatment plans of 20 patients from RTOG 0236. They observed an increase in isocentric dose in all patients following the application of heterogeneity corrections. However, the mean volume of PTV receiving 60 Gy decreased from 95 to 85 %, and dose to 95 % of the tumor decreased by an average of 4.7 Gy [67]. Based on these findings, the use of heterogeneity corrections would be associated with larger hot spot doses but worsened overall tumor coverage, potentially leading to increased complications due to the high-dose areas and higher potential for failure due to underdosing parts of the tumor. This led the investigators to conclude that the RTOG standard dose should in fact be 18 Gy per fraction delivered to the 95 % isodose, for a total dose of 54 Gy. Notably, these patients all had peripherally located tumors.

Investigators at the University of Maryland repeated this work on patients with peripherally and centrally located lung tumors. This study shows that dose to the internal target volume (ITV) increases with the application of heterogeneity corrections and the effect was even greater with centrally located tumors and larger. In centrally located tumors, where more lung parenchyma is located between tumor and body surface, intervening tissue density is overestimated. When this is corrected, dose to the tumor increases, an effect observed in this study. This too is true of larger tumors, where increased beam widths traverse more parenchyma prior to reaching the PTV. Given the data above, the inclusion of central tumors in this sample may in part explain why the application of heterogeneity corrections led to an increase in D ₉₅ in this study, versus a drop in D ₉₅ as observed in the paper by Xiao et al. [67], in which central tumors were excluded.

Without heterogeneity corrections applied to treatment plans, a higher dose must be prescribed to achieve adequate dose to the tumor, which also results in a higher dose to the surrounding parenchyma. This increases the risk of adverse outcomes, which may help to explain the increased complications seen in the initial Indiana experience. Based on these results, the use of heterogeneity corrections allows the prescription of a lower total dose and dose per fraction, with a comparable dose to the tumor. This less aggressive dose prescription may allow safer yet equally efficacious treatment of NSCLCs.

The placement of a diagnostic CT scanner in the treatment room with a known geometric relationship to the linear accelerator is one approach for volumetric imaging immediately prior to treatment with the patient in their immobilization device. Uematsu et al. have used this approach to treat liver and lung cancers with SBRT. Uematsu et al. reported that with repeat CT for frameless head and neck cancer radiotherapy, there was a geometric vector error ranging from 0.1 to 0.9 mm [70]. Multiple manufacturers have developed products of this type, including Siemens’ Primatrom, Mitsubishi’s accelerator in combination with a General Electric CT scanner, and Varian’s ExaCT targeting system [71–73]. All systems place the CT scanner in close proximity to the linear accelerator, allowing the couch to be moved from the imaging position to the treatment position. The CT scanner gantry is often translated during acquisition to minimize couch motion. Accuracy has been reported to be under 0.5 mm [72], and it has been reported to be improved with fiducial markers from 0.7 to 0.4 mm [71].

Advantages of in-room CT include that state of the art, diagnostic-quality CT can be used for optimal image quality and robustness. Disadvantages of this system are that the imaging and treatment isocenters are not coincident. Accuracy of motion from the CT scanner gantry, the accelerator couch, and the coincidence of the CT and linear accelerator isocenters needs to be verified. Limiting patient movement between imaging and treatment (e.g., couch retraction <1 mm) should improve setup accuracy; however, organ motion between imaging and delivery may occur.

Jaffray et al. [74] first described the concept of cone beam CT (CBCT) for image-guided radiation therapy in 1997. CBCT refers to combined kV X-ray imaging and MV radiation delivery in one integrated gantry-mounted system. Advancements in large-area flat panel detector technology facilitated volumetric imaging to be acquired in a single rotation of the linear accelerator gantry. Planar kV images projections are obtained as the gantry rotates about the patient on the linear accelerator table, over 30 s to 4 min. CBCT three-dimensional volume reconstruction images may then be obtained for position verification or for image guidance (see Fig. 13.2). Geometric calibration methodologies for CBCT systems [75] and quality assurance recommendations [74] have recently been proposed.

Doses delivered to obtain CBCT scans typically range from 0.5 to 2 cGy. Two vendors have developed kV CBCT systems: Elekta Synergy and Varian Trilogy and TrueBeam. In addition to providing volumetric imaging for verification and guidance, these systems have the ability to be used for real-time kV tracking; the latter application has not been used clinically.

Similar to in-room CT, artifacts may occur with kV CBCT reconstructions due to high Z structures such as surgical clips, hip prostheses, and dental fillings. Methods to reduce these artifacts have been developed.

CT imaging using MV beams has also been explored for more than 20 years [76, 77] and has also been made possible with advances in portal imaging technology. Advantages of MV cone beam CT are that the treatment MV beam is used to obtain the imaging, requiring less modification to the linear accelerator; the electron density estimates for treatment planning are accurate; and there is no high Z artifact that is associated with kV imaging.

MV cone beam CT has been used to aid in lung cancer SBRT, as described by Nakagawa et al. in 2000. MV CT-aided lung SBRT was used for treatment of 22 lung tumors [78].

Pouliot et al. recently reported the feasibility of acquiring low-exposure megavoltage CBCT. Phantom and pig cadaver head and neck images were acquired using a linear accelerator dose rate of 0.01–0.08 MU per image, for a set of 90–180 projections, acquired in 1–2° increments over 45–60 s. MV cone beam CT scans were obtained with doses of approximately 5 cGy. Despite the low efficiency of this system, visibility of high-contrast structures, such as air and bone, was reasonable [79].

MV TomoTherapy combines tomographic scanning capabilities, from a conventional CT detector, with a linear accelerator mounted on a rotating gantry. Simpson described the initial development of an MV CT scanner for radiation therapy in 1982 [76]. More recently, the TomoTherapy treatment platform has become available for image guidance and verification. The MV treatment beam is used to obtain imaging, with a lower energy, 3.5 MV instead of 6 MV. Computer-controlled multileaf collimators, also on the rotating gantry, have two sets of leaves that open and close to modulate the radiation beam while the couch advances the patient through the gantry bore, for helical intensity-modulated radiation therapy (IMRT).

Similar to MV cone beam CT, there are no high Z artifacts with MV TomoTherapy.

Real-time tumor tracking while the radiation beam is on is another approach to reduce adverse effects of organ motion. An elegant highly integrated tracking system consisting of four ceiling-mounted fluoroscopic X-ray tubes and four floor-mounted flat panel imagers in the treatment room allowing visualization of radiopaque markers in tumors was first described by Shirato et al. [58]. This system has a temporal resolution of 30 frames per second and a precision of 1.5 mm. The linear accelerator is triggered to irradiate only when the fiducial marker is located within a predefined volume. This system has been used for image-guided radiation therapy of lung, liver, and paraspinal malignancies.

As an alternative to turning the radiation beam off when the tumor moves outside the treatment region, multileaf collimators, the couch position, or the entire accelerator on a robotic arm may move with the tumor to ensure adequate tumor coverage (e.g., CyberKnife image-guided radiosurgery system). The latter lightweight (330 lb) linear accelerator mounted on a robotic arm uses 6 MV, 5- to 60-mm collimators, and a dose rate of 300–400 MU per minute, combined with dual orthogonal fluoroscopy tubes to track radiopaque markers in or near the tumor at a preset frequency. When the beam is on, infrared external surrogates are continuously monitored, while the internal anatomy is monitored every few seconds with kV imaging. The external surrogates are used for determining the breathing model, and the model is updated based on the X-ray data obtained every few seconds. The robotic linear accelerator responds to motion by moving to an appropriate position, within a range of ±10 mm x, y, z and ±1° pitch and roll, ±3° yaw. This system was found to have a 0.3-mm accuracy when tested in phantom studies. Disadvantages of this system include the need for fiducial markers, long potential delivery times (up to 90 min), lack of suitability for large tumors with motion more than 10 mm, and highly inhomogeneous dose distributions.

Another system (Novalis: BrainLAB, Heimstetten, Germany) also acquires kV orthogonal images and matches the images to DRRs obtained from the planning CT. The imaging axes are not coincident with isocenter, and a translation of patient position is required between imaging and treatment. Accuracy of this system has been reported to be within 3 % and 3-mm distance to agreement.

Recently, wireless transponders and infrared cameras to track tumors have also been proposed as an imageless localization system (Calypso Medical Technologies, Seattle, WA).

Since SBRT gives very high dose and uses much smaller planning margin than conventional therapy, more caution must be given to avoid catastrophic dose delivery. The patient safety has got more and more attention in radiation therapy society. Recently, the ASTRO SRS/SBRT white paper was published to address SRS/SBRT quality and safety considerations. This chapter presented the personnel requirement and training for radiation oncologist, medical physicist, medical dosimetrist, radiation therapist, and administrator; presented the technology requirements of simulation, planning, and localization; and addressed the SRS/SBRT system acceptance and commissioning.

The report of AAPM TG101 also has recommendations for SBRT patient safety issue. It recommends that at least one qualified medical physicist presents during first fraction of SBRT treatment and the qualified medical physicist should be available for the following fractions. It also recommends that the radiation oncologist should approve the image guidance before each fraction treatment. The therapist should be well trained for the SBRT procedure.

The equipment of SBRT mainly include the linac system and imaging system. The QA frequency is daily, monthly, and annually. Usually the radiation therapist performs the daily QA and the qualified physicist reviews and approves it, and the qualified physicist performs the monthly and annual QA. Apparently SBRT linac has tighter tolerance than the linac only for conventional therapy. The report of AAPM Task Group 142 [80] published recommendations for SRS/SBRT linac QA. The main recommendations about accuracy tolerance are summarized here. It recommends that the laser, the couch movement indictor, collimator size indicator, collimator rotation isocenter, couch rotation isocenter, gantry rotation isocenter, and coincidence of radiation and mechanical isocenter have to be within 1 mm. The couch rotation indictor has to be within 0.5°. The imaging system includes kV/MV imaging and kV/MV cone beam CT. It recommends that the imaging and treatment coordinate coincidence should be within 1 mm. For cone beam CT, the geometric distortion should be within 1 mm, and the contrast, spatial resolution, HU constancy, uniformity, and noise should agree with the baseline.

This approach is widely accepted as the current standard of care for peripheral T1 or T2 tumors or certain T3 tumors (i.e., invading the chest wall) which measure less than 5–7 cm without any nodal involvement. Central lesions may have a higher complication rate in comparison to peripheral tumors based on the initial phase II experience published out of Indiana [8]. In their single institution experience, “excessive toxicity” was reported for patients with tumors located within 2 cm of the proximal respiratory tree where the rate of grade 3 and above toxicity was significantly higher among patients with central tumors. This increase in toxicity may be related to dose and dose per fraction. Stephans et al. [84] reported the experience at Cleveland Clinic, which clearly illustrates the effects of the higher biologic effective dose (BED) on morbidity. Their institutional practice of SBRT initially used 10 Gy × 5 fractions and subsequently changed to the RTOG standard (18–20 Gy × 3) when RTOG 0236’s results were initially reported. The local control rates showed no difference between the two schemas, although they did experience a high rate of chest wall morbidity with the higher BED regimen (18 % versus 4 %, p = 0.028). In addition, follow-up from the initial Indiana experience treating central tumors reported lower grade 3 and higher side effects when >3 fractions were used as opposed to three fraction (26.3 % versus 7.7 %) [85]. However, caution is still indicated. Washington University [86] has completed a phase I study demonstrating 60 Gy in five fractions is safe for treating central tumors and is currently accruing to a phase II study. Many retrospective series also suggest a five fraction is safe in treating centrally located tumors [87]. In addition, a multi-institutional phase I/II [88] RTOG study is currently nearing completion using a similar fractionation schedule as the Washington University. Led by Videtic et al. [88] from the Cleveland Clinic, the RTOG has currently completed testing two less aggressive schemas (12 Gy × 4 fractions and 34 Gy × 1 fraction) in a randomized phase II trial, specifically looking at morbidity at 1 year as the primary end point as local control is expected to be 90 % in both arms (RTOG 0813). The less aggressive regimen will then be compared to the current RTOG standard which is a subsequent phase III trial. There is no lower limit of lung function based on pulmonary function tests that predicts poor outcomes [89]. One clinical entity that may have a higher risk of pulmonary injury is patients with interstitial pulmonary fibrosis. Onishi et al. [90] described 24 patients who died of fatal pneumonitis in the large multi-institutional experience. Seventeen of the 24 patient had IPF with 1 of the patients with usual interstitial pneumonia. The absolute risk of fatal pneumonitis for this cohort of patients in Japan is not known, but from Washington University described a 20 % risk of pneumonitis in patients with IPF. So a diagnosis of IPF is not a contraindication for SBRT but does appear to be at a higher risk of pneumonitis.

During the CT simulation, 3-mm slice thickness or less is preferred. IV contrast may be helpful for tumors close to the brachial plexus or for central tumors adjacent to vasculature. The gross tumor volume (GTV) is contoured on pulmonary windows, although soft tissue windows are helpful for tumors adjacent to the chest wall and central lesions. Contouring all the spiculations on lung windows is controversial and not uniformly performed. At the University of Maryland, only the bulky component of the spiculation is contoured (2-mm thickness) based on unpublished literature suggesting that it is uncommon that these radiographic findings correlate with clinically significant disease and is covered with subclinical doses in the area of dose falloff [61]. There are institutional preferences regarding the use of a margin for microscopic extension and creation of a CTV. In RTOG 0236, it was specified that the GTV was equivalent to the CTV. Assessment of respiratory motion and creation of an ITV is preferred to limit the PTV margins similar to SRS in the brain. The ITV can be assessed with a 4D CT scan or with fluoroscopy to track the tumor or a fiducial implanted into the tumor. A margin of 0.5 cm to create the PTV from the ITV is common. If an ITV is not created, population-based margins of 0.5 cm axially and 1.0 cm in the cranio-caudal directions were used historically in the Indiana experience and RTOG 0236. However, the use of patient-specific tumor motion is preferred. This can be performed by fusing maximum inspiration and expiration breath-hold scans to a free breathing CT, obtain a “slow” CT simulation, if 4D CT is not available. 4D CT has been demonstrated to result in smaller PTV volumes than any of the other described options [91]. If there is significant respiratory motion, some have advocated for managing this with abdominal compression or breath-hold maneuvers. The benefit of abdominal compression is likely to be greatest for lower lobe tumors. However, abdominal compression may increase tumor motion in some cases and should be considered on an individual basis and there are several studies which demonstrate increased failure with the use of abdominal compression and gating [92]. At the University of Maryland, a CTV margin of 3 mm is added based on the unpublished work from Fox Chase Cancer Center which evaluated 25 consecutive patients who underwent a lobectomy or sublobar resection for a curative procedure for tumors <3 cm in maximum dimension and also had a diagnostic CT scan for review. Based on a comparison of CT and microscopic pathology review, the entire microscopic extent of disease was covered when 3 mm was added to the maximum extent of the disease contoured on standard lung windows without chasing the spiculations in 95 % of the cases. An additional 3 mm was added for setup error based on obtaining a daily CBCT prior to each treatment.

Interfraction setup variation is reduced with image-guided radiotherapy (IGRT). This can be performed by matching fiducial location, which is vital to technologies which do not use volumetric IGRT, and/or creating a CBCT with the patient immobilized. These pretreatment images are compared to the simulation images and adjusted as appropriate. Fusion of the CBCT with the simulation CT using bony anatomy is recommended, as there is minimal change in the target centroid position relative to the skeletal frame [93]. The differences in patient position based on matching with bony anatomy versus soft tissue can be off by upwards of 8 mm on average but this is primary based on our medically inoperable patients who are likely to have emphysema and poorly functioning diaphragms [94]. Alignment using soft tissue can be performed if imaging acquired on cone beam imaging is similar to that generated by the 4D CT-based ITV. If the volumes do not match, then the treating physician needs to consider that the patient’s breathing pattern may be different from the day of the initial 4D CT. This difference may not be reflected accurately on the CBCT and alignment based on soft tissue may therefore be inaccurate potentially leading to a geographic miss. In this situation, a bony alignment is preferable and treatment can be delivered if the volume is safely within the PTV on the CBCT. If it is outside the volume, a repeat 4D CT is preferred.

At the University of Maryland, consideration of the accuracy of cone beam imaging is considered to be 2 mm such that a shift will be performed only if the shift is 3 mm or more based on the work from Princess Margaret Hospital [95].

SBRT/SABR has been most widely studied in primary and metastatic lung cancer. A summary of clinical data is shown in Tables 13.1 and 13.2 and some of the major studies are discussed in greater detail below.