Credentialing of vertebral stereotactic ablative body radiotherapy in a multi-centre trial

Purpose/objectiveStereotactic ablative body radiotherapy (SABR) in multi-centre trials requires rigorous quality assurance to ensure safe and consistent treatment for all trial participants. We report results of vertebral SABR dosimetry credentialing for the ALTG/TROG NIVORAD trial.Material/methodsCentres with a previous SABR site visit performed axial film measurement of the benchmarking vertebral plan in a local phantom and submitted radiochromic film images for analysis. Remaining centres had on-site review of SABR processes and axial film measurement of the vertebral benchmarking plan. Films were analysed for dosimetric and positional accuracy: gamma analysis (>90% passing 2%/2mm/10% threshold) and ≤ 1 mm positional accuracy at target-cord interface was required.Results19 centres were credentialed; 11 had on-site measurement. Delivery devices included linear accelerator, TomoTherapy and CyberKnife systems. Five centres did not achieve 90% gamma passing rate. Of these, three were out of tolerance (OOT) in low (<5Gy) dose regions and > 80% passing rate and deemed acceptable. Two were OOT over the full dose range: one elected not to remeasure; the other also had positional discrepancy greater than 1 mm and repeat measurement with a new plan was in tolerance. The original OOT was attributed to inappropriate MLC constraints. All centres delivered planned target-cord dose gradient within 1 mm.ConclusionCredentialing measurements for vertebral SABR in a multi-centre trial showed although the majority of centres delivered accurate vertebral SABR, there is high value in independent audit measurements. One centre with inappropriate MLC settings was detected, which may have resulted in delivery of clinically unacceptable vertebral SABR plans.     

On the use of AAA and AcurosXB algorithms for three different stereotactic ablative body radiotherapy (SABR) techniques: Volumetric modulated arc therapy (VMAT), intensity modulated radiation therapy (IMRT) and 3D conformal radiotherapy (3D-CRT)

AimThe purpose of this study was to investigate the dosimetric characteristics of three stereotactic ablative body radiotherapy (SABR) techniques using the anisotropic analytical algorithm (AAA) and Acuros XB algorithm. The SABR techniques include coplanar volumetric modulated arc therapy (C-VMAT), non-coplanar intensity modulated radiation therapy (NC-IMRT) and non-coplanar three-dimensional conformal radiotherapy (NC-3D CRT).BackgroundSABR is a special type of radiotherapy where a high dose of radiation is delivered over a short time. The treatment outcome and accuracy of the dose delivered to cancer patients highly depend on the dose calculation algorithm and treatment technique.Materials and methodsTwelve lung cancer patients underwent 4D CT scanning, and three different treatment plans were generated: C-VMAT, NC-IMRT, NC-3D CRT. Dose calculation was performed using the AAA and Acuros XB algorithm. The dosimetric indices, such as conformity index (CI), homogeneity index, dose fall-off index, doses received by organs at risk and planning target volume, were used to compare the plans. The accuracy of AAA and Acuros XB (AXB) algorithms for the lung was validated against measured dose on a CIRS thorax phantom.ResultsThe CIs for C-VMAT, NC-IMRT and NC-3D CRT were 1.21, 1.28 and 1.38 for the AAA, respectively, and 1.17, 1.26 and 1.36 for the Acuros XB algorithm, respectively. The overall dose computed by AcurosXB algorithm was close to the measured dose when compared to the AAA algorithm. The overall dose computed by the AcurosXB algorithm was close to the measured dose when compared to the AAA algorithm.ConclusionThis study showed that the treatment planning results obtained using the Acuros XB algorithm was better than those using the AAA algorithm in SABR lung radiotherapy.     

The impact of respiratory gating on lung dosimetry in stereotactic body radiotherapy for lung cancer

The purpose of this study was to evaluate the impacts of respiratory gating and different gating windows (GWs) on lung dosimetry in stereotactic body radiotherapy (SBRT) for lung cancer.Gated SBRT plans were developed using the four-dimensional computed tomography data from 17 lung cancer patients treated with SBRT. Using amplitude-based end-exhalation gating, we established 2 fixed GWs with approximate duty cycles of 50% (50% GW) and 25% (25% GW), respectively, for this study.For highly mobile tumors (3D mobility > 10 mm), additional benefits in lung-dose reductions were achieved with the 25% GW, as a result of inadequate mobility and planning target volume reductions obtained with the 50% GW. In these tumors, the absolute differences compared to the non-gated and 50% gated plans, were 0.5 Gy and 0.33 Gy for the mean lung dose and 1.11% and 0.71% for the V20, respectively. Dosimetric benefits were achieved with the 50% GW, compared with the non-gated plan, for tumors with both low mobility and small volume (gross tumor volume ≤ 10 cc). Among the identified predictive factors of dosimetric benefits, the lateral distance from midspinal canal and the motion range in anterior–posterior direction might be stronger factors because of their correlations with many of the lung-dose parameters and greater predictive capacity.The results of the present study might facilitate the selection of appropriate patients and the optimal GW according to the tumor characteristics for gated lung SBRT.     

Geometrical and dosimetrical uncertainties in hypofractionated radiotherapy of the lung: A review

The application of high precision hypofractionated regimes (a.k.a. stereotactic body radiotherapy (SBRT)) to the treatment of lung cancer is a ‘success story’ of radiotherapy. From the technical perspective, lung SBRT is a challenging technique as all aspects of the treatment workflow, from imaging to dose calculation to treatment delivery, should be carefully handled in order to ensure consistency between planned and delivered dose.In this review such technical aspects are presented and discussed, looking at what has been developed over the years.The use of imaging techniques such as slow-CT, breath-hold CT, four-dimensional CT and mid-ventilation is reviewed, presenting the main characteristics of each approach but not necessarily to single out ‘the best’ solution.Concerning dose calculation, a number of studies clearly separate dose algorithms that should be considered inadequate for lung SBRT (e.g. simple pencil beam algorithms) from approaches such as convolution algorithms, Monte Carlo, and solution of the transport equation, that are much better at handling the combination of small fields and heterogenenous geometries that make dose calculation not trivial.Patient positioning and management of intrafraction motion have been two areas of significant developments, to the point where it is difficult to identify which solution represents the best compromise between technical complexity and clinical effectiveness. The review analyses several of these methods, outlining the residual uncertainties associated with each of them.Last but not least, two subjects are discussed, adaptive therapy and particle therapy, that may represent in the near future additional tools for the technical improvement of lung SBRT.     

Clinical verification of treatment planning dose calculation in lung SBRT with GATE Monte Carlo simulation code

PurposeThis study aims to use GATE/Geant4 simulation code to evaluate the performance of dose calculations with Anisotropic Analytical Algorithm (AAA) in the context of lung SBRT for complex treatments considering images of patients.MethodsFour cases of non-small cell lung cancer treated with SBRT were selected for this study. Irradiation plans were created with AAA and recalculated end to end using Monte Carlo (MC) method maintaining field configurations identical to the original plans. Each treatment plan was evaluated in terms of PTV and organs at risk (OARs) using dose-volume histograms (DVH). Dosimetric parameters obtained from DVHs were used to compare AAA and MC.ResultsThe comparison between the AAA and MC DVH using gamma analysis with the passing criteria of 3%/3% showed an average passing rate of more than 90% for the PTV structure and 97% for the OARs. Tightening the criteria to 2%/2% showed a reduction in the average passing rate of the PTV to 86%. The agreement between the AAA and MC dose calculations for PTV dosimetric parameters (V₁₀₀; V₉₀; Homogeneity index; maximum, minimum and mean dose; CI_Paddick and D_2cm) was within 18.4%. For OARs, the biggest differences were observed in the spinal cord and the great vessels.ConclusionsIn general, we did not find significant differences between AAA and MC. The results indicate that AAA could be used in complex SBRT cases that involve a larger number of small treatment fields in the presence of tissue heterogeneities.     

Predictive value of vascular calcification identified in 4D planning CT of lung cancer patients treated with stereotactic body radiation therapy

PurposeThe aim was to identify vascular calcification in 4DCT scan of lung cancer patients and establish the association between overall survival (OS) and vascular calcification, as surrogate for vascular health.MethodsVascular calcification within the thoracic cavity were segmented in 334 lung cancer patients treated with stereotactic body radiation therapy (SBRT). This has been done automatically on 4D planning CT and average reconstruction scans. Correlation between cardiac comorbidity and calcification volumes was evaluated for patients with recorded Adult Co-Morbidity Evaluation (n = 303). Associations between the identified calcifications and OS were further investigated.ResultsThe volume of calcification from the average scan was significantly lower than from each phase (p < 0.001). The highest level of correlations between cardiac comorbidity and volume of the calcifications were found for one phase representing inhale and two phases representing exhale with the least motion blurring due to respiration (p < 0.005). The volume of the calcifications was subsequently averaged over these three phases. The average of calcification volumes over the three phases (denoted by inhale-exhale) showed the highest likelihood in univariate analysis and was chosen as vascular calcification measure. Cox-model suggested that tumor volume (Hazard Ratio [HR] = 1.46, p < 0.01) and inhale-exhale volume (HR = 1.05, p < 0.05) are independent factors predicting OS after adjusting for age, sex, and performance status.ConclusionIt was feasible to use. It 4DCT scan for identifying thoracic calcifications in lung cancer patients treated with SBRT. Calcification volumes from inhale-exhale phases had the highest correlation with overall cardiac comorbidity and the average of the calcification volume obtained from these phases was an independent predictive factor for OS.     

Survival outcome after stereotactic body radiotherapy for locally advanced and borderline resectable pancreatic cancer: A systematic review and meta-analysis

BackgroundSome studies reported stereotactic body radiotherapy (SBRT) has demonstrated superior therapeutic results than conventional radiotherapy. Nevertheless, this statement is controversial and the trial attempting to prove this is underway. We conducted this systemic review and meta-analysis aiming to combine the latest and most complete information about the survival outcomes and toxicities following SBRT for locally advanced pancreatic cancer (LAPC) and borderline resectable pancreatic cancer (BRPC).MethodsItems involving SBRT and pancreatic cancer were searched in PubMed, EMBASE, Cochrane Library, SCOPUS and Web of Science. Median overall survival (OS), 1/2/3-year OS, median progression-free survival (PFS), 1/2/3-year PFS and incidence of grade 3–5 toxicities were the endpoints of interest in this meta-analysis. These endpoint proportions were pooled and analyzed using R.ResultsFor the LAPC series, the median OS was 14.1 months; pooled 1/2/3-year OS rates were 57%, 19% and 10%, respectively; the median PFS was 10 months; pooled 1/2/3-year PFS rates were 36%, 12% and 4%; pooled incidence rates of acute gastrointestinal (GI), acute hematologic and late GI toxicity (grade≥3) were 2%, 4% and 8%. For the BRPC series, the median OS was 17.5 months; pooled 1/2-year OS rates were 75% and 29%; the median PFS was 12.2 months; pooled 1/2-year PFS rates were 48% and 18%; the incidence rates of toxicity (grade ≥ 3) were all 0%.ConclusionsOur meta-analysis based on published results of OS, PFS and incidence rates of toxicity demonstrated that SBRT does not show desirable therapeutic result than the standard therapies for LAPC and BRPC.     

Evaluation of the target dose coverage of stereotactic body radiotherapy for lung cancer using helical tomotherapy: A dynamic phantom study

AimTo evaluate the target dose coverage for lung stereotactic body radiotherapy (SBRT) using helical tomotherapy (HT) with the internal tumor volume (ITV) margin settings adjusted according to the degree of tumor motion.BackgroundLung SBRT with HT may cause a dosimetric error when the target motion is large.Materials and methodsTwo lung SBRT plans were created using a tomotherapy planning station. Using these original plans, five plans with different ITV margins (4.0–20.0 mm for superior-inferior [SI] dimension) were generated. To evaluate the effects of respiratory motion on HT, an original dynamic motion phantom was developed. The respiratory wave of a healthy volunteer was used for dynamic motion as the typical tumor respiratory motion. Five patterns of motion amplitude that corresponded to five ITV margin sizes and three breathing cycles of 7, 14, and 28 breaths per minute were used. We evaluated the target dose change between a static delivery and a dynamic delivery with each motion pattern.ResultsThe target dose difference increased as the tumor size decreased and as the tumor motion increased. Although a target dose difference of <5 % was observed at ≤10 mm of tumor motion for each condition, a maximum difference of -9.94 % ± 7.10 % was observed in cases of small tumors with 20 mm of tumor motion under slow respiration.ConclusionsMinimizing respiratory movement is recommended as much as possible for lung SBRT with HT, especially for cases involving small tumors.     

Local control of 1–5 fraction radiotherapy regimens for spinal metastases: an analysis of the impacts of biologically effective dose and primary histology

BackgroundThis analysis evaluates the impacts of biologically effective dose (BED) and histology on local control (LC) of spinal metastases treated with highly conformal radiotherapy to moderately-escalated doses.Materials and methodsPatients were treated at two institutions from 2010–2020. Treatments with less than 5 Gy per fraction or 8 Gy in 1 fraction were excluded. The dataset was divided into three RPA classes predictive of survival (1). The primary endpoint was LC.Results223 patients with 248 treatments met inclusion criteria. Patients had a median Karnofsky Performance Status (KPS ) of 80, and common histologies included breast (29.4%), non-small cell lung cancer (15.7%), and prostate (13.3%). A median 24 Gy was delivered in 3 fractions (BED: 38.4 Gy) to a median planning target volume (PTV) of 37.3 cc. 2-year LC was 75.7%, and 2-year OS was 42.1%. Increased BED was predictive of improved LC for primary prostate cancer (HR = 0.85, 95% CI: 0.74–0.99). Patients with favorable survival (RPA class 1) had improved LC with BED ≥ 40 Gy (p = 0.05), unlike the intermediate and poor survival groups. No grade 3–5 toxicities were reported.ConclusionsModerately-escalated treatments were efficacious and well-tolerated. BED ≥ 40 Gy may improve LC, particularly for prostate cancer and patients with favorable survival.     

High-dose neoadjuvant chemoradiotherapy versus chemotherapy alone followed by surgery in potentially-resectable stage IIIA-N2 NSCLC. A multi-institutional retrospective study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society)

BackgroundThe optimal induction treatment in potentially-resectable stage IIIA-N2 NSCLC remains undefined.AimTo compare neoadjuvant high-dose chemoradiotherapy (CRT) to neoadjuvant chemotherapy (CHT) in patients with resectable, stage IIIA-N2 non-small-cell lung cancer (NSCLC).MethodsRetrospective, multicentre study of 99 patients diagnosed with stage cT1-T3N2M0 NSCLC who underwent neoadjuvant treatment (high-dose CRT or CHT) followed by surgery between January 2005 and December 2014.Results47 patients (47.5%) underwent CRT and 52 (52.5%) CHT, with a median follow-up of 41 months. Surgery consisted of lobectomy (87.2% and 82.7%, in the CRT and CHT groups, respectively) or pneumonectomy (12.8% vs. 17.3%). Nodal downstaging (to N1/N0) and Pathologic complete response (pCR; pT0pN0) rates were significantly higher in the CRT group (89.4% vs. 57.7% and 46.8% vs. 7.7%, respectively; p < 0.001)). Locoregional recurrence was significantly lower in the CRT group (8.5% vs. 13.5%; p = 0.047) but distant recurrence rates were similar in the two groups. Median PFS was 45 months (CHT) vs. “not reached” (CRT). Median OS was similar: 61 vs. 56 months (p = 0.803). No differences in grade ≥3 toxicity were observed. On the Cox regression analysis, advanced pT stage was associated with worse OS and PFS (p < 0.001) and persistent N2 disease (p = 0.002) was associated with worse PFS.ConclusionsCompared to neoadjuvant chemotherapy alone, a higher proportion of patients treated with preoperative CRT achieved nodal downstaging and pCR with better locoregional control. However, there were no differences in survival. More studies are needed to know the optimal treatment of these patients.     

Radiotherapy for the treatment of pituitary adenomas: A dosimetric comparison of three planning techniques

AimOur goal was to compare conformal 3D (C3D) radiotherapy (RT), modulated intensity RT (IMRT), and volumetric modulated arc therapy (VMAT) planning techniques in treating pituitary adenomas.BackgroundRT is important for managing pituitary adenomas. Treatment planning advances allow for higher radiation dosing with less risk of affecting organs at risk (OAR).Materials and methodsWe conducted a 5-year retrospective review of patients with pituitary adenoma treated with external beam radiation therapy (C3D with flattening filter, flattening filter-free [FFF], IMRT, and VMAT). We compared dose-volume histogram data. For OARs, we recorded D2%, maximum, and mean doses. For planning target volume (PTV), we registered V95%, V107%, D95%, D98%, D50%, D2%, minimum dose, conformity index (CI), and homogeneity index (HI).ResultsFifty-eight patients with pituitary adenoma were included. Target-volume coverage was acceptable for all techniques. The HI values were 0.06, IMRT; 0.07, VMAT; 0.08, C3D; and 0.09, C3D FFF (p < 0.0001). VMAT and IMRT provided the best target volume conformity (CI, 0.64 and 0.74, respectively; p < 0.0001). VMAT yielded the lowest doses to the optic pathway, lens, and cochlea. The position of the neck in extreme flexion showed that it helps in planning mainly with VMAT by allowing only one arc to be used and achieving the desired conformity, decreasing the treatment time, while allowing greater protection to the organs of risk using C3D, C3DFFF.ConclusionsOur results confirmed that EBRT in pituitary adenomas using IMRT, VMAT, C3D, C3FFF provide adequate coverage to the target. VMAT with a single arc or incomplete arc had a better compliance with desired dosimetric goals, such as target coverage and normal structures dose constraints, as well as shorter treatment time. Neck extreme flexion may have benefits in treatment planning for better preservation of organs at risk. C3D with extreme neck flexion is an appropriate treatment option when other treatment techniques are not available.     

Retrospective assessment of a single fiducial marker tracking regimen with robotic stereotactic body radiation therapy for liver tumours

AimTo investigate tumour motion tracking uncertainties in the CyberKnife Synchrony system with single fiducial marker in liver tumours.BackgroundIn the fiducial-based CyberKnife real-time tumour motion tracking system, multiple fiducial markers are generally used to enable translation and rotation corrections during tracking. However, sometimes a single fiducial marker is employed when rotation corrections are not estimated during treatment.Materials and methodsData were analysed for 32 patients with liver tumours where one fiducial marker was implanted. Four-dimensional computed tomography (CT) scans were performed to determine the internal target volume (ITV). Before the first treatment fraction, the CT scans were repeated and the marker migration was determined. Log files generated by the Synchrony system were obtained after each treatment and the correlation model errors were calculated. Intra-fractional spine rotations were examined on the spine alignment images before and after each treatment.ResultsThe mean (standard deviation) ITV margin was 4.1 (2.3) mm, which correlated weakly with the distance between the fiducial marker and the tumour. The mean migration distance of the marker was 1.5 (0.7) mm. The overall mean correlation model error was 1.03 (0.37) mm in the radial direction. The overall mean spine rotations were 0.27° (0.31), 0.25° (0.22), and 0.23° (0.26) for roll, pitch, and yaw, respectively. The treatment time was moderately associated with the correlation model errors and weakly related to spine rotation in the roll and yaw planes.ConclusionsMore caution and an additional safety margins are required when tracking a single fiducial marker.