|Ahead of print publication
Setting up a lung stereotactic body radiotherapy service in a tertiary center in Eastern India: The process, quality assurance, and early experience
Raj Kumar Shrimali1, Animesh Saha2, Balakrishnan Arun3, Sriram Prasath3, Chandran Nallathambi3, Suchandana Bhoumik3, Indranil Mallick3, Rimpa Basu Achari3, Sanjoy Chatterjee3
1 Department of Radiation Oncology, Tata Medical Center, Kolkata, West Bengal, India; Department of Clinical Oncology, Arden Cancer Centre, University Hospitals Coventry and Warwickshire NHS Trust, Clifford Bridge Road, Coventry, CV2 2DX, UK
2 Department of Radiation Oncology, Tata Medical Center, Kolkata, West Bengal, India; Department of Clinical Oncology, St. James's University Hospital, Leeds LS97TF, UK
3 Department of Radiation Oncology, Tata Medical Center, Kolkata, West Bengal, India
St James's University Hospital, Leeds Teaching Hospital NHS Trust, Beckett street, Leeds, LS85AJ
Source of Support: None, Conflict of Interest: None
Context: Stereotactic body radiotherapy (SBRT) is increasingly being used for early-stage lung cancer and lung oligometastases.
Aims: To report our experience of setting up lung SBRT and early clinical outcomes.
Settings and Design: This was a retrospective, interventional, cohort study.
Subjects and Methods: Patients were identified from multidisciplinary tumor board meetings. They underwent four-dimensional computed tomography-based planning. The ROSEL trial protocol, the Radiation Therapy Oncology Group (RTOG) 0236, and the UK-Stereotactic Ablative Body Radiotherapy Consortium guidelines were used for target volume and organs-at-risks (OARs) delineation, dosimetry, and plan quality assessment. Each SBRT plan underwent patient-specific quality assurance (QA). Daily online image guidance using KVCT or MVCT was done to ensure accurate treatment delivery.
Statistical Analysis Used: Microsoft Excel 2010 was used for data analysis.
Results: Fifteen patients were treated to one or more lung tumors. One patient received helical tomotherapy in view of bilateral lung oligometastases at similar axial levels. All the remaining patients received volumetric modulated arc therapy (VMAT)-based treatment. The prescription dose varied from 40 to 60 Gy in 5–8 fractions with alternate-day treatment. The mean and median lung V20 was 5.24% and 5.16%, respectively (range, 1.66%–9.10%). The mean and median conformity indexes were 1.02 and 1.06, respectively (range, 0.70–1.18). After a median follow-up of 17 months, the locoregional control rate was 93.3%.
Conclusions: SBRT was implemented using careful evaluation of OAR dose constraints, dosimetric accuracy and plan quality, patient-specific QA, and online image guidance for accurate treatment delivery. It was safe and effective for early-stage nonsmall cell lung cancer and lung metastases. Prospective data were collected to audit our outcomes.
Keywords: Cone-beam computed tomography, four-dimensional computed tomography, lung cancer, stereotactic body radiotherapy, volumetric modulated arc radiotherapy
|How to cite this URL:|
Shrimali RK, Saha A, Arun B, Prasath S, Nallathambi C, Bhoumik S, Mallick I, Achari RB, Chatterjee S. Setting up a lung stereotactic body radiotherapy service in a tertiary center in Eastern India: The process, quality assurance, and early experience. J Can Res Ther [Epub ahead of print] [cited 2019 Aug 23]. Available from: http://www.cancerjournal.net/preprintarticle.asp?id=263535
| > Introduction|| |
Nonsmall cell lung cancer (NSCLC) is the most common cause of cancer death in the world. Surgical resection has been the standard treatment for early-stage NSCLC, with 5-year overall survival (OS) rate ranging from 60% to 70%., Surgical resection is also widely used for lung oligometastases from other primary tumors, and several surgical series have reported favorable outcomes with a 5-year OS of up to 69%, in carefully selected patients. However, many patients are deemed medically inoperable and are offered radiation therapy. Conventionally fractionated external-beam radiation therapy is associated with high rates of local recurrence and poor long-term survival. The role of stereotactic body radiotherapy (SBRT) is gradually and increasingly being established for patients with early-stage NSCLC as well as for oligometastatic lung disease, who are inoperable for medical reasons.,, SBRT is also emerging as a reasonable alternative option for operable Stage I NSCLC.,,, SBRT is defined as a technique for delivering accurate and precise external-beam radiotherapy to an extracranial target, using high doses per fraction, in 1–8 treatment fractions., SBRT protocols are convenient for the patient and offer durable local control with low reported rates of toxicity. SBRT has been reported to result in high rates of local control (85%–90%) with a 5-year survival rate of about 70% for patients with early-stage NSCLC , and is gaining acceptance for the treatment of patients with low-volume oligometastatic disease who have a good performance status. SBRT treatment for lung tumor can be delivered in multiple ways, including fixed-field (static) intensity-modulated radiotherapy (FF IMRT), helical tomotherapy (HT), and volumetric modulated arc therapy (VMAT).,,,, We report our experience of setting up lung SBRT using rotational IMRT (VMAT and HT), based on the current literature and available guidelines. We also describe our process from patient selection to treatment planning and delivery, listing the potential challenges we faced, and hints that we believe would be helpful for other centers that are in the process of setting-up their SBRT service. We also present our quality assurance (QA) data and early clinical outcomes.
| > Subjects and Methods|| |
Evidence reviewed before setting up our lung SBRT service include the UK-Stereotactic Ablative Body Radiotherapy (SABR) Consortium guidelines, the ROSEL protocol, the Radiation Therapy Oncology Group (RTOG) 0236 trial, and other relevant literature.,,,,
Patient selection criteria
These have been adapted from study protocols of the RTOG 0236 and the ROSEL trial., Each patient is carefully discussed in the lung multidisciplinary team meeting, and eligibility for SBRT is decided.
- Diagnosis of cancer (NSCLC or metastasis) based on findings of positive histology or a positive positron emission tomography (PET) scan, if biopsy not possible
- Not suitable for surgery because lesion is technically inoperable, or significant medical comorbidity, or where the patient declined surgery
- The WHO performance status 0–2
- Peripheral lesions outside a 2 cm radius of main airways and proximal bronchial tree
- Age >18 years
- Appropriate staging with PET-computed tomography (CT) for T1 N0 M0 or T2 (≤5 cm) N0 M0 or low volume oligometastatic disease in the lung based on positive histology or PET scan. This must be solitary metachronous metastasis with the primary site in remission or well controlled.
- Any patient not meeting all of the above inclusion criteria
- Primary tumors involving the mediastinal structures or central T3 primary tumors. Tumors within 2 cm radius of main airways and proximal bronchial tree
- Multiple lung metastases (3 or more)
- Oligometastases with uncontrolled primary
- Any tumor that is not clinically definable on the treatment planning CT scan, e.g., surrounded by consolidation or atelectasis
- If tumor has respiratory motion ≥1 cm despite using techniques to reduce tumor motion, only proceed with treatment if target delineation is reliable and suggested normal tissue and tumor planning constraints can be achieved
- Previous radiotherapy within the planned treatment volume (PTV).
Pretreatment assessment includes CT-guided core biopsy, PET-CT scan for staging, magnetic resonance imaging brain (essential for NSCLC), pulmonary function tests (forced expiratory volume in 1 s in liters and as percentage of predicted value), gas transfer factor (DLCO), and routine blood tests (blood counts and biochemical profile). However, poor lung functions or diagnosis of COPD is not absolute contraindications, if the patient can cooperate and lie flat on the treatment couch for a reasonable duration of time.,,
Patient setup and planning four-dimensional computed tomography acquisition
For radiotherapy planning, we use a dedicated wide-bore 16-slice CT scanner (GE LightSpeed Xtra; GE, Milwaukee, Wisconsin, USA). Our preferred position for simulation is supine with arms above the head (or holding a pole). The position has to be both comfortable and reproducible. It is assessed that patients can maintain the treatment position for a reasonable period (at least 30 min); otherwise, they are deemed unsuitable for SBRT. It may be necessary to immobilize the patient in a 5-point shell for apical tumor. As we use VMAT for treatment planning and delivery, an arms-down (by the side) position could be a concern, and partial arcs with avoidance sectors would be considered in patients who are in a 5-point shell. After the patient is positioned on the CT couch, a surrogate for respiratory motion is used to establish the breathing signal. For motion detection and management, we use the Varian real-time position management (RPM) system (RPM version 1.7.5, Varian Medical Systems, Palo Alto, CA, USA). This system typically consists of a camera emitting infrared light and a plastic block (the RPM box) with reflective markers. Breathing pattern (rate, rhythm, and regularity) is assessed initially using the RPM box and verbally coaching the patient. Patients are then tattooed at a stable point at approximately the midline in the superior-inferior axis and two lateral tattoos at approximately the level of the likely isocenter position. The couch is positioned so that the external lasers align with the origin tattoos and radiopaque markers taped to the patient to indicate the scan origin. Typically, two image sets are taken: a free breathing scout film and a four-dimensional CT (4DCT) with free breathing. The 4DCT scan is acquired in 2.5-mm slices (120 kV, 40 mAs) using our defined protocol from the jaw or the cricoid to L2 vertebra. We ensure inclusion of the whole liver for right-sided lower lobe tumors. Then, the acquired images are exported to the dedicated GE workstation for reconstruction and phase-based binning (GE Workstation, AW Volume Share 4, GE, Milwaukee, Wisconsin, USA). The physicist supervises the phase-based binning of the acquired 4DCT dataset and the redistribution into 10 phase-bins called 0%–90% phases.
The reconstructions typically consist of the following:
- A maximum intensity projection (MIP) image that will show the entire motion envelope of the tumor, which is used to delineate the internal target volume (ITV),
- An average intensity projection (Av-IP) image, which is an average image over all phases. This dataset is used for planning and dose calculation.,
- Patients unable to maintain a regular breathing cycle are likely to have problems with their 4DCT, resulting in significant phase errors during binning and reconstruction. These patients should be identified immediately and directed to receiving a helical (fast) CT scan and a slow axial CT scan for motion assessment and margins
- The cine duration of axial CT acquisition (imaging beam-on time) at each couch position depends on the rate of breathing, and the number of phase-based bins decided for each breathing cycle. We divide the breathing cycle into 10 phase-bins. The observed breathing time required for one complete breathing cycle (60 Seconds/ Respiratory rate) is added to 1 second, to obtain the duration of acquisition at each couch position. This ensures adequate sampling of all image slices at each phase of the respiratory signal
- The interscan duration is the time from the end of the previous image acquisition to the beginning of the next. During this time, the imager beam is off. This time is used for couch movement and stabilization and is long enough to ensure that the vibrations in the tissues cease. We typically use 1.3 s for this
- The data used to generate the 4DCT scan may be edited before image reconstruction in response to slight irregularities in the breathing cycle. The patient must remain in the department, while the scan is being reconstructed, and until the physicist and radiation oncologist is satisfied with the image quality of the reconstructions
- The imaging datasets are manually checked for errors, artifacts, and inaccurate reconstruction by the physicist and radiation oncologist. One should also look for discontinuities in anatomy or any unusual features. This check must be carried out on each of the 10 phases, MIP, and Av-IP images. There should be no major artifacts near the tumor or at the levels of the anticipated PTV
- To consider rescanning using 4DCT if the patient can breathe regularly, but has momentary irregularity (such as cough or hiccough). However, if the patient is unable to breathe regularly for a sufficient period of time (i.e., >2–3 min), during the initial assessment, 4DCT should not be attempted at all
- If scan reconstruction is not possible or full of artifacts because of breathing irregularities, then helical (fast) CT scan and a slow axial CT scan will be acquired.
Contouring and dose prescription
The target volume and organs-at-risks (OARs) delineation also follow standard guidance from the RTOG and ROSEL protocols and the UK SABR Consortium guidelines.,, The target volumes are outlined as follows:
- Gross tumor volume (GTV) – The GTV is described as the radiologically visible tumor in the lung
- Clinical target volume (CTV) – The CTV is identical to the ITV in almost all situations, with no additional margin for microscopic disease extension. It is believed that at hypofractionated doses used in SBRT, the high-dose penumbra takes care of the microscopic disease. The relevance of CTV is limited to situations where a helical 3DCT has to be used for planning
- ITV – The ITV is the composite tumor volume (including the motion envelope) obtained using a 4DCT scan. This is defined as tumor contoured using the MIP dataset, and subsequently visually confirmed that the visible tumor lies within the boundaries of the MIP-delineated target volume on all respiratory phases (0% to 90%) on axial, coronal, and sagittal views 
- Planning target volume (PTV) – ITV is expanded to PTV using a standard isotropic 5-mm margin to account for setup errors.
The prescription dose varied from 40 to 60 Gy in 5–8 fractions. OARs include the following: spinal cord, esophagus, heart with pericardium, trachea and proximal bronchial tree, whole lung, and brachial plexus. Delineation and dose constraints used for OARs are generally according to ROSEL trial protocol and UK SABR Consortium guidelines [Table 1].,, We outline the brachial plexus as described by Hall et al. Proximal trachea contour begins 10 cm superior to superior extent of PTV or 5 cm superior to the carina (whichever is the more superior) and continue inferiorly to the superior aspect of the proximal bronchial tree. Proximal bronchial tree includes the most distal 2 cm of trachea, carina, right and left main-stem bronchi, right and left upper lobe bronchi, the bronchus intermedius (right), right middle lobe bronchus, lingular bronchus (left), and the right and left lower lobe bronchi. Contouring of the lobar bronchi ends immediately at the site of a segmental bifurcation. For adhering to the strict eligibility requirement for excluding patients with tumors in the zone of the proximal bronchial tree, an artificial structure 2 cm larger in all directions from the trachea and the proximal bronchial tree is drawn (no fly zone) for each patient.
- After the ITV is contoured, a check should be carried out that the tumor is completely within the ITV, in all of the datasets corresponding to the different phase-bins
- In practice, part of the PTV is allowed to overlap with the no fly zone, but not the GTV or ITV.
VMAT (RapidArc) plans are created using the Eclipse Treatment Planning System (version 10.0.42, Varian Medical Systems, Palo Alto, CA, USA),,,, while HT plans are created using the HiArt Tomotherapy Treatment Planning Platform (TomoTherapy Inc., Madison, WI, USA).,, In the contouring module, the PTV, OARs, overlapping structures (OS) of OARs, non-OSs, ring structures around PTV, and dummy structures are verified before planning. VMAT plans are typically created using two or three partial arcs or semiarcs according to the tumor location. The direction of gantry rotation is decided such that successive arcs alternate between clockwise and anticlockwise movement to increase the planning and treatment delivery efficiency. The arcs are of appropriate field size and typically have a complimentary collimator angle 30°–45° with each other for clockwise and anticlockwise motion. In the optimization module, constraints to the target, objectives to the OARs, and varying priorities and penalties are assigned to achieve the desired and acceptable dose optimization curves for the target and for the OARs. After dose calculations, the plans are evaluated. Dose-volume histograms (DVH) are also reviewed for dose coverage and OARs. Any hotspots, underdosed areas, and dose spill are controlled using dose priorities assigned to pseudostructures in those areas, in the subsequent optimization followed by dose calculation.
With tomotherapy planning, the PTV and the OS are declared as target constraints, and the rest are in the regions at risk constraints with the dose constraints, importance, overlap priority, and maximum and minimum dose penalties. In helical delivery, there are three main parameters used in planning. These are longitudinal extent of treatment field width (equal to the axial thickness of the fan beam), pitch (equal to the distance the couch travels per gantry rotation relative to the field width at the axis of rotation), and the modulation factor (MF) (equal to the maximum leaf opening time relative to the average leaf opening time). We use a field width of 1 cm, pitch of 0.1, and MF of 2.2, and the prescription given is set such that 95% of PTV will receive the full 60 Gy in five fractions. Once the desired optimization is achieved, the full dose and final dose are calculated to get the scattering contributions and to get final accurate dose distributions.
- Subsequent to planning and dosimetry, the OARs should be visually inspected to ensure that wherever a treatment arc passes through an OAR, it has been contoured completely
- The body outline should also be contoured wherever an arc is traversing it.
Plan quality evaluation
For all of the treatment plans, the plan quality is evaluated by reviewing the dose distribution and calculating selected dosimetric indices for the PTV and OARs from each DVH., For the PTV, plan conformality is assessed using three indices, i.e., volume (100%)/volume (PTV), volume (50%)/volume (PTV), and maximum dose to >2 cm of PTV. Conformality of the prescription dose to the target volume is assessed using the ICRU conformity index (CI) which is defined as ratio of prescription isodose volume to the PTV. A CI value closest to 1.0 indicates better conformity of dose to the target. Intermediate dose spillage and fall-off gradient beyond the PTV are assessed using two indices: volume (50%)/volume (PTV) and maximum dose to >2 cm of PTV. Volume (50%)/volume (PTV) is the ratio of 50% prescription isodose volume to the PTV, whereas maximum dose >2 cm is the maximum dose (percentage of nominal prescription dose) at least 2 cm from the PTV in any direction. Lower volume (50%)/volume (PTV) and lower maximum dose >2 cm indicate greater dose fall-off and better plan conformity. In addition, the global maximum dose for each plan is also observed and recorded. With respect to OARs, the maximum dose index to the spinal cord, esophagus, heart, trachea, and proximal bronchial tree is tracked, while for lung, the V20 and V12.5 (percentage volume of total lung minus ITV receiving 20 Gy or 12.5 Gy) are recorded. Homogeneity index (HI) is also calculated for plan comparison and documentation. HI is defined as ratio of D5% and D95% where D5% and D95% are the minimum doses delivered to 5% and 95% of the PTV, respectively., Values of HI closest to one indicate greater homogeneity within the target. The dose conformity requirements and the dose constraints to the OARs are adapted from the ROSEL trial protocol. The dose constraints for the 5-fraction regime are also used for the eight fraction regimes (erring on the cautious side).
Radiotherapy plan quality assurance
Our patient-specific QA for the SBRT plans includes point dose measurement and fluence pattern testing. This also enables a check that all beams/arcs are deliverable, without collision with the couch. The verification plans for VMAT are created in the eclipse treatment planning system. For coronal plane fluence verification, we use the 729 2D-array, placed in the Octavius phantom supplied by PTW. For point dose measurement, we use the A1SL pinpoint ion chamber placed in the cheese phantom. The measured fluence is compared with the coronal plane dose fluence calculated from the treatment planning system. The 729 2D array in the Octavius phantom is read using the verisoft PTW software to determine gamma pass rate (criteria: 3% max dose difference, 3 mm distance to agreement, passed gamma evaluation >95% dose points)., Passing criteria for point dose measurement is within ±3% dose deviation between the TPS calculated point dose and the measured point dose in the calibrated A1SL ion chamber within the cheese phantom. On two occasions, the point dose deviation was >3% probably because the point of measurement was in an area of steep dose gradient. As the deviation was in the negative direction (i.e., the point was under-dosed), it was felt to be safe and was accepted by the radiation oncologist. However, the point dose variation was still within ±5% for all the patients, and gamma pass rates for all patients were >96%, demonstrating that each treatment was delivered with acceptable accuracy.
Patient-specific QA on tomotherapy, for the approved patient plan, is done in the delivery QA (DQA) module. Point dose verification is carried out using calibrated A1SL ion chamber and the fluence pattern is verified using EBT3 Gafchromic film placed at the coronal plane level in the cheese phantom. The irradiated film is scanned in the flatbed scanner and the tiff image is imported into the DQA module. The gamma and line profile of the fluence is compared between the measured and TPS calculated values. The tolerance for deviation of point dose between TPS calculated dose and measured dose within ±3% is acceptable. Gamma profile of the fluence is evaluated by visually verifying the color coding assigned value of blue, yellow to red color.
Treatment is delivered using daily online image guidance. KV cone-beam CT (CBCT) is used for VMAT, and MVCT is used for HT. Verification image is matched to the planning CT by experienced radiographers, concentrating both on bony (vertebral body) alignment and evaluation of soft-tissue positioning of lung tumor. If the visible tumor on CBCT is within the ITV, then no shift is carried out.
- When the tumor is not far from the central structures, the initial matching must be with the spine, to ensure safety, as all of the major OARs (except brachial plexus) are also centrally placed. Then, the coverage of the tumor is assessed. Any subsequent lateral shift is carefully monitored, as they could potentially bring the OARs closer to the treatment isodose curves
- After the treatment is completed, a final CBCT is carried out, to identify any intra-fraction shift.
The interfraction interval should be at least 40 h  and is typically 48 h using alternate-day treatments, with a maximum interval of 4 days between the treatment fractions. We aim for the overall treatment for five fractions to be completed within 2 weeks and for any 8-fraction treatment to be completed within 3 weeks.
After completion of the treatment, patients are followed up monthly for the first 3 months. Response assessment contrast-enhanced CT (CECT) scan of the thorax is done at 3 months. Thereafter, the patients are followed at three monthly intervals for next 2 years and then 6 monthly for the subsequent 3 years. Repeat CECT will be done yearly once or earlier if the patient is symptomatic.
| > Results|| |
Patient's characteristics are summarized in [Table 2]. We have treated 15 patients with SBRT to one or more tumors, with one patient who received SBRT twice to different nodules in his right lung. All of them were male except two. The median age was 71 years (range: 62–80 years). Nine of them have primary NSCLC (one of them had a second lung primary) and six had lung oligometastatic disease from another primary. Two of the patients with lung metastases had one lesion in both lungs and were treated simultaneously, making the treatment planning more challenging. The mean and median PTV volumes were 37.86 cc and 30.8 cc, respectively (range: 5.49 cc to 84.7 cc). All patients had 4DCT-based treatment simulation and planning. Fourteen patients were treated using VMAT and one patient with bilateral lung oligometastases was treated with HT. The prescription dose varied from 40 to 60 Gy in 5–8 fractions with alternate-day treatment. Treatment was delivered with daily online image guidance where KV-CBCT was used for VMAT and MVCT was used in tomotherapy.
Dose constraints for OARs were met for all of the patients [Table 1]. The mean and median lung V20 was 5.24% and 5.16%, respectively (range: 1.66%–9.10%). The mean and median lung V12.5 was 8.74% and 8.92%, respectively (range: 3.24%–16.13%). Dose conformity achieved for PTV is also summarized in [Table 1]. The mean and median CI was 1.02 and 1.06, respectively, and ranged between 0.7 and 1.18. The mean and median HI was 1.10 and 1.06, respectively, and ranged from 1.04 to 1.24. The patient-specific QA data for all of the 16 treatment plans for 15 patients are presented in [Table 3].
Two patients underwent simultaneous treatment of two lung lesions. One patient had bilateral lung oligometastases at different axial levels, and therefore, it was not anticipated that there would be any overlapping of the two different coplanar plans and the ensuing dose distributions. This patient was treated with two different plans for each of these target volumes [Figure 1]. The other patient received HT in view of bilateral lung oligometastases at similar axial levels and was treated with a single plan treating both target volumes [Figure 2]. The two patients are described together in [Table 4].
|Figure 1: Treatment of two metastatic lesions at different axial levels using two separate volumetric modulated arc radiotherapy plans|
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|Figure 2: Treatment of two metastatic lesions at the same axial level using Helical TomoTherapy|
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At 3 months posttreatment, one patient had complete response, six had partial response, eight had stable disease, and one patient has progressed distally on CT Thorax. None of the patients have developed any acute or late toxicity, including radiation pneumonitis, brachial plexopathy, esophagitis, myelopathy, or cardiac toxicity. At a median follow-up of 17 months, 11 patients have controlled disease (locally and distally), and four patients have disease progression with distant metastases including one with local and distant progression.
| > Discussion|| |
With improvements in radiation technology, a number of groups began to investigate the use of hypofractionated SABR for lung tumors, both primary NSCLC and metastatic carcinomas. Major guidelines including the ESMO Clinical Practice Guidelines now consider SBRT as the first-line nonsurgical treatment option for medically inoperable Stage I NSCLC.,, SBRT is an attractive alternative therapy for the following several reasons: outpatient treatment, noninvasive, 20–30 min per treatment, short overall treatment time (1–2 weeks), no sedation or anesthesia required, painless, immediate return to activities, being therefore highly desirable for elderly patients. SBRT is feasible and safe even for elderly patients, patients with COPD and poor lung functions.,
One of the major challenges to setting up the service includes the absence of data from completed randomized phase-III trials. Therefore, the best available evidence was obtained from meta-analyses and systemic reviews of nonrandomized data from various single-arm studies and retrospective series. As these numerous studies differ from each other, the data are heterogeneous. The dilemma about the wide variety is listed below and summarized in [Table 5] and [Table 6]:
- Diversity in motion management approaches and margins 
- Diversity in dose fractionation schemes – various fractionation schedules have been used, ranging from a single to ten or more fractions., Various dose fractionations have been suggested in literature, i.e., standard dose fractionation: 18 Gy × 3 fractions, conservative dose fraction: 12 Gy × 5 fractions or 11 Gy × 5 fractions and very conservative dose fractionation: 50–60 Gy in 8–10 fractions ,,,,
- Confusion regarding prescription point – To the isocenter, structure (PTV), or a named isodose
- Diversity in planning techniques (coplanar or noncoplanar, fields or arcs (full/partial/multiple), whether flattening filter-free portals should be used): There has been an increase in use of IMRT to treat SBRT of the lung,, yet these different types of IMRT have not been fully evaluated
- Diversity in treatment techniques (linear accelerators, cyberknife, tomotherapy): Most centers around the world use linear accelerators.,,
Our prescription dose varied from 40 to 60 Gy in 5–8 fractions with alternate day treatment. Although a biologically equivalent dose (BED) of ≥100 Gy10 is used for SBRT for early-stage NSCLC,, a study by Janssen et al., showed that SBRT with a BED <90 Gy10 could also yield high local control rates and no significant toxicity. Therefore, lower dose SBRT appears a reasonable option for Stage I NSCLC in selected patients aged >70 years and those presenting in a reduced general condition. In our study, 16 out of 18 lesions in 15 patients were treated with a BED of ≥100 Gy10[Table 2]. Among the various IMRT techniques (i.e., FF-IMRT, VMAT, and HT) used for lung SBRT treatments, HT has been shown to be better dosimetrically when compared to seven-field coplanar IMRT and two-arc coplanar RA, reducing maximum rib dose, as well as improving dose conformity and uniformity. One of our SBRT patients was treated using HT as he had bilateral lung metastases, both of which were in upper lobe near brachial plexus, and we wanted to treat both of these lesions with a single plan. Our OAR dose constraints were adapted from the ROSEL study, RTOG, and UK SABR Consortium guideline,,, and we were able to meet the OAR constraints for all of our patients. These dose limits are based on the highest dose/fractionation regimes reported to be safe in lung SABR and therefore should be safe for lower biological equivalent dose regimes used. The conformality of lung SBRT plan has been evaluated in the RTOG 0236 and 0618 protocols, where plan acceptability was defined as a CI <1.2. Plan heterogeneity is not as important as long as doses exceeding 100% of the prescription remain within the PTV. Our dose conformity requirement was based on ROSEL trial protocol and UK SABR Consortium guidelines , and was met for all the plans. Plan homogeneity was quite acceptable with a mean and median value of 1.10 and 1.06 (range: 1.04–1.24).
The gamma-index method suggested by Low et al. is generally used for comparing 2D fluence pattern for IMRT patient's specific QA, and IMRT plans are evaluated with gamma passing rates. The criterion of 3%/3 mm has typically been used for gamma evaluation for VMAT QA with tolerance of 10%.,, Recent studies have raised the question of whether or not the criterion of 3%/3 mm for VMAT QA is clinically relevant., Fredh et al. compared VMAT QA results of four different commercial dosimeters and concluded that a criterion of 2%/2 mm rather than 3%/3 mm should be used clinically. Out of 16 SBRT plans for 15 patients in the current series, 13 plans met the 3% criteria, and seven plans satisfied the 2% criteria. For VMAT and HT patient-specific QA, we have checked the 2D fluence pattern as well as point dose. As per our institutional protocol, we follow gamma index evaluation with the criteria of 3% max dose difference, 3 mm distance to agreement and gamma pass rate of >95%. Point dose variations of our patients were within ±5% and gamma pass rates were >96% for all the patients. Two patients had a deviation of the point dose measurement at −4.6% and −4.7%, which were accepted because they were in the negative direction (and therefore deemed to be safe). These points were found to be situated in an area of steep dose gradient, making interpretation of the point dose difficult.
Further challenges after treatment include how to follow-up these patients. There is evolving data on tumor response assessment imaging., It is well recognized that very conformal RT using hypofractionated doses can lead to very conformal fibrosis. CT may not be optimal and might lead to confusion, as increased local fibrosis can raise the suspicion of recurrence. In a series by Takeda et al., only 3 out of 20 patients suspected on CT had recurrence. The role of FDG-PET is evolving in this setting; however, this may have a different challenge – inflammation versus metabolic response to explain a higher uptake of FDG., Out of our 15 lung SBRT patients, 11 patients have locally controlled disease at a median follow-up of 17 months with a good quality of life and no major toxicity. Four patients have progressed distally.
| > Conclusion|| |
SBRT is safe and effective for early-stage NSCLC and lung metastases. Most single-arm phase-II and retrospective studies show excellent local control. However, before setting up a lung SBRT service, it is important to understand the pitfalls and to carefully evaluate the challenges before deciding on the local protocol. Careful evaluation of planning quality, OAR dose constraints, dosimetric accuracy, and accurate treatment delivery are necessary. A thorough review of the relevant current evidence considering all aspects of this treatment modality is essential.
The authors acknowledge the untiring effort of all the radiographers in the lung SBRT setting up process.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Coleman MP, Forman D, Bryant H, Butler J, Rachet B, Maringe C, et al.
Cancer survival in Australia, Canada, Denmark, Norway, Sweden, and the UK, 1995-2007 (the International Cancer Benchmarking Partnership): An analysis of population-based cancer registry data. Lancet 2011;377:127-38.
Deslauriers J. Current surgical treatment of nonsmall cell lung cancer 2001. Eur Respir J Suppl 2002;35:61s-70s.
Allen MS, Darling GE, Pechet TT, Mitchell JD, Herndon JE 2nd
, Landreneau RJ, et al.
Morbidity and mortality of major pulmonary resections in patients with early-stage lung cancer: Initial results of the randomized, prospective ACOSOG Z0030 trial. Ann Thorac Surg 2006;81:1013-9.
Kim S, Ott HC, Wright CD, Wain JC, Morse C, Gaissert HA, et al.
Pulmonary resection of metastatic sarcoma: Prognostic factors associated with improved outcomes. Ann Thorac Surg 2011;92:1780-6.
Nanda RH, Liu Y, Gillespie TW, Mikell JL, Ramalingam SS, Fernandez FG, et al.
Stereotactic body radiation therapy versus no treatment for early stage non-small cell lung cancer in medically inoperable elderly patients: A national cancer data base analysis. Cancer 2015;121:4222-30.
Ahmed KA, Torres-Roca JF. Stereotactic body radiotherapy in the management of oligometastatic disease. Cancer Control 2016;23:21-9.
Siva S, MacManus M, Ball D. Stereotactic radiotherapy for pulmonary oligometastases: A systematic review. J Thorac Oncol 2010;5:1091-9.
Hurkmans CW, Cuijpers JP, Lagerwaard FJ, Widder J, van der Heide UA, Schuring D, et al.
Recommendations for implementing stereotactic radiotherapy in peripheral stage IA non-small cell lung cancer: Report from the quality assurance working party of the randomised phase III ROSEL study. Radiat Oncol 2009;4:1.
Chang JY, Senan S, Paul MA, Mehran RJ, Louie AV, Balter P, et al.
Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: A pooled analysis of two randomised trials. Lancet Oncol 2015;16:630-7.
Shirvani SM, Jiang J, Chang JY, Welsh J, Likhacheva A, Buchholz TA, et al.
Lobectomy, sublobar resection, and stereotactic ablative radiotherapy for early-stage non-small cell lung cancers in the elderly. JAMA Surg 2014;149:1244-53.
Yu JB, Soulos PR, Cramer LD, Decker RH, Kim AW, Gross CP. Comparative effectiveness of surgery and radiosurgery for stage I non-small cell lung cancer. Cancer 2015;121:2341-9.
Chang BK, Timmerman RD. Stereotactic body radiation therapy: A comprehensive review. Am J Clin Oncol 2007;30:637-44.
Timmerman RD, Park C, Kavanagh BD. The North American experience with stereotactic body radiation therapy in non-small cell lung cancer. J Thorac Oncol 2007;2:S101-12.
Onishi H, Araki T. Stereotactic body radiation therapy for stage I non-small-cell lung cancer: A historical overview of clinical studies. Jpn J Clin Oncol 2013;43:345-50.
Fakiris AJ, McGarry RC, Yiannoutsos CT, Papiez L, Williams M, Henderson MA, et al.
Stereotactic body radiation therapy for early-stage non-small-cell lung carcinoma: Four-year results of a prospective phase II study. Int J Radiat Oncol Biol Phys 2009;75:677-82.
Timmerman RD, Kavanagh BD, Cho LC, Papiez L, Xing L. Stereotactic body radiation therapy in multiple organ sites. J Clin Oncol 2007;25:947-52.
Holt A, van Vliet-Vroegindeweij C, Mans A, Belderbos JS, Damen EM. Volumetric-modulated arc therapy for stereotactic body radiotherapy of lung tumors: A comparison with intensity-modulated radiotherapy techniques. Int J Radiat Oncol Biol Phys 2011;81:1560-7.
Weyh A, Konski A, Nalichowski A, Maier J, Lack D. Lung SBRT: Dosimetric and delivery comparison of RapidArc, tomoTherapy, and IMR. J Appl Clin Med Phys 2013;14:4065.
Casutt A, Bouchaab H, Beigelman-Aubry C, Bourhis J, Lovis A, Matzinger O. Stereotactic body radiotherapy with helical tomoTherapy for medically inoperable early stage primary and second-primary non-small-cell lung neoplasm: 1-year outcome and toxicity analysis. Br J Radiol 2015;88:20140687.
Rosen LR, Fischer-Valuck BW, Katz SR, Durci M, Wu HT, Syh J, et al.
Helical image-guided stereotactic body radiotherapy (SBRT) for the treatment of early-stage lung cancer: A single-institution experience at the Willis-Knighton Cancer Center. Tumori 2014;100:42-8.
Fitzgerald R, Owen R, Hargrave C, Pryor D, Barry T, Lehman M, et al.
A comparison of three different VMAT techniques for the delivery of lung stereotactic ablative radiation therapy. J Med Radiat Sci 2016;63:23-30.
Timmerman R, Galvin J, Michalski J, Straube W, Ibbott G, Martin E, et al.
Accreditation and quality assurance for radiation therapy oncology group: Multicenter clinical trials using stereotactic body radiation therapy in lung cancer. Acta Oncol 2006;45:779-86.
Distefano G, Baker A, Scott AJ, Webster GJ; UK SABR Consortium Quality Assurance Group. Survey of stereotactic ablative body radiotherapy in the UK by the QA group on behalf of the UK SABR consortium. Br J Radiol 2014;87:20130681.
Louie AV, Rodrigues G, Hannouf M, Lagerwaard F, Palma D, Zaric GS, et al
. Withholding stereotactic radiotherapy in elderly patients with stage I non-small cell lung cancer and co-existing COPD is not justified: Outcomes of a markov model analysis. Int J Radiat Oncol Biol Phys 2011;81:581.
Palma D, Lagerwaard F, Rodrigues G, Haasbeek C, Senan S. Curative treatment of stage I non-small-cell lung cancer in patients with severe COPD: Stereotactic radiotherapy outcomes and systematic review. Int J Radiat Oncol Biol Phys 2012;82:1149-56.
Guckenberger M, Kestin LL, Hope AJ, Belderbos J, Werner-Wasik M, Yan D, et al.
Is there a lower limit of pretreatment pulmonary function for safe and effective stereotactic body radiotherapy for early-stage non-small cell lung cancer? J Thorac Oncol 2012;7:542-51.
Underberg RW, Lagerwaard FJ, Cuijpers JP, Slotman BJ, van Sörnsen de Koste JR, Senan S, et al.
Four-dimensional CT scans for treatment planning in stereotactic radiotherapy for stage I lung cancer. Int J Radiat Oncol Biol Phys 2004;60:1283-90.
Underberg RW, Lagerwaard FJ, Slotman BJ, Cuijpers JP, Senan S. Use of maximum intensity projections (MIP) for target volume generation in 4DCT scans for lung cancer. Int J Radiat Oncol Biol Phys 2005;63:253-60.
Glide-Hurst CK, Chetty IJ. Improving radiotherapy planning, delivery accuracy, and normal tissue sparing using cutting edge technologies. J Thorac Dis 2014;6:303-18.
Hall WH, Guiou M, Lee NY, Dublin A, Narayan S, Vijayakumar S, et al
. Development and validation of a standardized method for contouring the brachial plexus: preliminary dosimetric analysis among patients treated with IMRT for head-and-neck cancer. Int J Radiat Oncol Biol Phys 2008;72:1362-7.
Morgan-Fletcher SL. Prescribing, Recording and Reporting Photon Beam Therapy (Supplement to ICRU Report 50), ICRU Report 62. ICRU, pp. ix+52, 1999 (ICRU Bethesda, MD) $65.00. Br J Radiol 2001;74:294.
Ezzell GA, Burmeister JW, Dogan N, LoSasso TJ, Mechalakos JG, Mihailidis D, et al.
IMRT commissioning: Multiple institution planning and dosimetry comparisons, a report from AAPM task group 119. Med Phys 2009;36:5359-73.
Wu QJ, Yoo S, Kirkpatrick JP, Thongphiew D, Yin FF. Volumetric arc intensity-modulated therapy for spine body radiotherapy: Comparison with static intensity-modulated treatment. Int J Radiat Oncol Biol Phys 2009;75:1596-604.
Ezzell GA, Galvin JM, Low D, Palta JR, Rosen I, Sharpe MB, et al.
Guidance document on delivery, treatment planning, and clinical implementation of IMRT: Report of the IMRT subcommittee of the AAPM radiation therapy committee. Med Phys 2003;30:2089-115.
Langen KM, Papanikolaou N, Balog J, Crilly R, Followill D, Goddu SM, et al.
QA for helical tomotherapy: Report of the AAPM task group 148. Med Phys 2010;37:4817-53.
Boily G, Filion É, Rakovich G, Kopek N, Tremblay L, Samson B, et al.
Stereotactic ablative radiation therapy for the treatment of early-stage non-small-cell lung cancer: CEPO review and recommendations. J Thorac Oncol 2015;10:872-82.
Vansteenkiste J, Crinò L, Dooms C, Douillard JY, Faivre-Finn C, Lim E, et al.
ESMO consensus conference on lung cancer: Early-stage non-small-cell lung cancer consensus on diagnosis, treatment and follow-up. Ann Oncol 2014;25:1462-74.
Nagata Y, Hiraoka M, Shibata T, Onishi H, Kokubo M, Karasawa K, et al.
Prospective trial of stereotactic body radiation therapy for both operable and inoperable T1N0M0 non-small cell lung cancer: Japan clinical oncology group study JCOG0403. Int J Radiat Oncol Biol Phys 2015;93:989-96.
Bral S, Gevaert T, Linthout N, Versmessen H, Collen C, Engels B, et al.
Prospective, risk-adapted strategy of stereotactic body radiotherapy for early-stage non-small-cell lung cancer: Results of a phase II trial. Int J Radiat Oncol Biol Phys 2011;80:1343-9.
Koto M, Takai Y, Ogawa Y, Matsushita H, Takeda K, Takahashi C, et al.
A phase II study on stereotactic body radiotherapy for stage I non-small cell lung cancer. Radiother Oncol 2007;85:429-34.
Baumann P, Nyman J, Hoyer M, Wennberg B, Gagliardi G, Lax I, et al.
Outcome in a prospective phase II trial of medically inoperable stage I non-small-cell lung cancer patients treated with stereotactic body radiotherapy. J Clin Oncol 2009;27:3290-6.
Lindberg K, Nyman J, Riesenfeld Källskog V, Hoyer M, Lund JŠ, Lax I, et al.
Long-term results of a prospective phase II trial of medically inoperable stage I NSCLC treated with SBRT – The nordic experience. Acta Oncol 2015;54:1096-104.
Ricardi U, Filippi AR, Guarneri A, Giglioli FR, Ciammella P, Franco P, et al.
Stereotactic body radiation therapy for early stage non-small cell lung cancer: Results of a prospective trial. Lung Cancer 2010;68:72-7.
Timmerman R, Paulus R, Galvin J, Michalski J, Straube W, Bradley J, et al.
Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA 2010;303:1070-6.
Nyman J, Hallqvist A, Lund JŠ, Brustugun OT, Bergman B, Bergström P, et al.
SPACE – A randomized study of SBRT vs. conventional fractionated radiotherapy in medically inoperable stage I NSCLC. Radiother Oncol 2016;121:1-8.
Zhang GG, Ku L, Dilling TJ, Stevens CW, Zhang RR, Li W, et al.
Volumetric modulated arc planning for lung stereotactic body radiotherapy using conventional and unflattened photon beams: A dosimetric comparison with 3D technique. Radiat Oncol 2011;6:152.
Ong CL, Verbakel WF, Cuijpers JP, Slotman BJ, Lagerwaard FJ, Senan S. Stereotactic radiotherapy for peripheral lung tumors: A comparison of volumetric modulated arc therapy with 3 other delivery techniques. Radiother Oncol 2010;97:437-42.
Ding C, Chang CH, Haslam J, Timmerman R, Solberg T. A dosimetric comparison of stereotactic body radiation therapy techniques for lung cancer: Robotic versus conventional linac-based systems. J Appl Clin Med Phys 2010;11:3223.
Chan MK, Kwong DL, Law GM, Tam E, Tong A, Lee V, et al.
Dosimetric evaluation of four-dimensional dose distributions of cyberKnife and volumetric-modulated arc radiotherapy in stereotactic body lung radiotherapy. J Appl Clin Med Phys 2013;14:4229.
Merna C, Rwigema JC, Cao M, Wang PC, Kishan AU, Michailian A, et al.
A treatment planning comparison between modulated tri-cobalt-60 teletherapy and linear accelerator-based stereotactic body radiotherapy for central early-stage non-small cell lung cancer. Med Dosim 2016;41:87-91.
Ewing MM, Desrosiers C, Fakiris AJ, DeBliek CR, Kiszka DN, Stinson ER, et al.
Conformality study for stereotactic radiosurgery of the lung. Med Dosim 2011;36:14-20.
Palma DA, Senan S, Haasbeek CJ, Verbakel WF, Vincent A, Lagerwaard F, et al.
Radiological and clinical pneumonitis after stereotactic lung radiotherapy: A matched analysis of three-dimensional conformal and volumetric-modulated arc therapy techniques. Int J Radiat Oncol Biol Phys 2011;80:506-13.
Merrow CE, Wang IZ, Podgorsak MB. A dosimetric evaluation of VMAT for the treatment of non-small cell lung cancer. J Appl Clin Med Phys 2012;14:4110.
Fitzgerald R, Owen R, Barry T, Hargrave C, Pryor D, Bernard A, et al.
The effect of beam arrangements and the impact of non-coplanar beams on the treatment planning of stereotactic ablative radiation therapy for early stage lung cancer. J Med Radiat Sci 2016;63:31-40.
Dong P, Lee P, Ruan D, Long T, Romeijn E, Low DA, et al.
4π noncoplanar stereotactic body radiation therapy for centrally located or larger lung tumors. Int J Radiat Oncol Biol Phys 2013;86:407-13.
Janvary ZL, Jansen N, Baart V, Devillers M, Dechambre D, Lenaerts E, et al.
Clinical outcomes of 130 patients with primary and secondary lung tumors treated with cyberknife robotic stereotactic body radiotherapy. Radiol Oncol 2017;51:178-86.
Burghelea M, Verellen D, Dhont J, Hung C, Gevaert T, Van den Begin R, et al.
Treating patients with dynamic wave arc:First clinical experience. Radiother Oncol 2017;122:347-51.
Ma SJ, Serra LM, Syed YA, Hermann GM, Gomez-Suescun JA, Singh AK, et al.
Comparison of single- and three-fraction schedules of stereotactic body radiation therapy for peripheral early-stage non-small-cell lung cancer. Clin Lung Cancer 2018;19:e235-40.
Wang Z, Li AM, Gao J, Li J, Li B, Lee P, et al.
Clinical outcomes of CyberKnife stereotactic radiosurgery for elderly patients with presumed primary stage I lung cancer. Transl Lung Cancer Res 2017;6:6-13.
Lagerwaard FJ, Haasbeek CJ, Smit EF, Slotman BJ, Senan S. Outcomes of risk-adapted fractionated stereotactic radiotherapy for stage I non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2008;70:685-92.
Videtic GM, Stephans K, Reddy C, Gajdos S, Kolar M, Clouser E, et al.
Intensity-modulated radiotherapy-based stereotactic body radiotherapy for medically inoperable early-stage lung cancer: Excellent local control. Int J Radiat Oncol Biol Phys 2010;77:344-9.
Distefano G, Lee J, Jafari S, Gouldstone C, Baker C, Mayles H, et al.
A national dosimetry audit for stereotactic ablative radiotherapy in lung. Radiother Oncol 2017;122:406-10.
Zhang J, Yang F, Li B, Li H, Liu J, Huang W, et al.
Which is the optimal biologically effective dose of stereotactic body radiotherapy for stage I non-small-cell lung cancer? A meta-analysis. Int J Radiat Oncol Biol Phys 2011;81:e305-16.
Janssen S, Kaesmann L, Rudat V, Rades D. Stereotactic body radiotherapy (SBRT) with lower doses for selected patients with stage I non-small-cell lung cancer (NSCLC). Lung 2016;194:291-4.
Wagner D, Vorwerk H. Two years experience with quality assurance protocol for patient related rapid arc treatment plan verification using a two dimensional ionization chamber array. Radiat Oncol 2011;6:21.
Low DA, Harms WB, Mutic S, Purdy JA. A technique for the quantitative evaluation of dose distributions. Med Phys 1998;25:656-61.
Davidson MT, Blake SJ, Batchelar DL, Cheung P, Mah K. Assessing the role of volumetric modulated arc therapy (VMAT) relative to IMRT and helical tomotherapy in the management of localized, locally advanced, and post-operative prostate cancer. Int J Radiat Oncol Biol Phys 2011;80:1550-8.
Nelms BE, Zhen H, Tomé WA. Per-beam, planar IMRT QA passing rates do not predict clinically relevant patient dose errors. Med Phys 2011;38:1037-44.
Zhen H, Nelms BE, Tome WA. Moving from gamma passing rates to patient DVH-based QA metrics in pretreatment dose QA. Med Phys 2011;38:5477-89.
Fredh A, Scherman JB, Fog LS, Munck af Rosenschöld P. Patient QA systems for rotational radiation therapy: A comparative experimental study with intentional errors. Med Phys 2013;40:031716.
Takeda A, Kunieda E, Fujii H, Yokosuka N, Aoki Y, Oooka Y, et al.
Evaluation for local failure by 18F-FDG PET/CT in comparison with CT findings after stereotactic body radiotherapy (SBRT) for localized non-small-cell lung cancer. Lung Cancer 2013;79:248-53.
Pastis NJ Jr., Greer TJ, Tanner NT, Wahlquist AE, Gordon LL, Sharma AK, et al.
Assessing the usefulness of 18F-fluorodeoxyglucose PET-CT scan after stereotactic body radiotherapy for early-stage non-small cell lung cancer. Chest 2014;146:406-11.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]