Juergen Wilbert

Is a single arc sufficient in volumetric-modulated arc therapy (VMAT) for complex-shaped target volumes?

PURPOSE To compare step-and-shoot intensity-modulated radiotherapy (ss-IMRT) with volumetric-modulated arc therapy (VMAT) for complex-shaped target volumes with a simultaneous integrated boost (SIB). MATERIALS AND METHODS This retrospective planning study was based on 20 patients composed of prostate cancer (n=5), postoperative (n=5) or primary (n=5) radiotherapy for pharyngeal cancer and for cancer of the paranasal sinuses (n=5); a SIB with two or three dose levels was planned in all patients. For each patient, one ss-IMRT plan with direct-machine-parameter optimization (DMPO) and VMAT plans with one to three arcs (SmartArc technique) were generated in the Pinnacle planning system. RESULTS Single arc VMAT improved target coverage and dose homogeneity in radiotherapy for prostate cancer. Two and three VMAT arcs were required to achieve equivalent results compared to ss-IMRT in postoperative and primary radiotherapy for pharyngeal cancer, respectively. In radiotherapy for cancer of the paranasal sinuses, multiarc VMAT resulted in increased spread of low doses to the lenses and decreased target coverage in the region between the orbits. CONCLUSIONS The complexity of the target volume determined whether single arc VMAT was equivalent to ss-IMRT. Multiple arc VMAT improved results compared to single arc VMAT at cost of increased delivery times, increased monitor unites and increased spread of low doses.

Dose–Response Relationship for Image-Guided Stereotactic Body Radiotherapy of Pulmonary Tumors: Relevance of 4D Dose Calculation

PURPOSE To evaluate outcome after image-guided stereotactic body radiotherapy (SBRT) for early-stage non-small-cell lung cancer (NSCLC) and pulmonary metastases. METHODS AND MATERIALS A total of 124 patients with 159 pulmonary lesions (metastases n = 118; NSCLC, n = 41; Stage IA, n = 13; Stage IB, n = 19; T3N0, n = 9) were treated with SBRT. Patients were treated with hypofractionated schemata (one to eight fractions of 6-26 Gy); biologic effective doses (BED) to the clinical target volume (CTV) were calculated based on four-dimensional (4D) dose calculation. The position of the pulmonary target was verified using volume imaging before all treatments. RESULTS With mean/median follow-up of 18/14 months, actuarial local control was 83% at 36 months with no difference between NSCLC and metastases. The dose to the CTV based on 4D dose calculation was closely correlated with local control: local control rates were 89% and 62% at 36 months for >100 Gy and <100 Gy BED (p = 0.0001), respectively. Actuarial freedom from regional and systemic progression was 34% at 36 months for primary NSCLC group; crude rate of regional failure was 15%. Three-year overall survival was 37% for primary NSCLC and 16% for metastases; no dose-response relationship for survival was observed. Exacerbation of comorbidities was the most frequent cause of death for primary NSCLC. CONCLUSIONS Doses of >100 Gy BED to the CTV based on 4D dose calculation resulted in excellent local control rates. This cutoff dose is not specific to the treatment technique and protocol of our study and may serve as a general recommendation.

Measurement of output factors for small photon beams

A variety of detectors and procedures for the measurement of small field output factors are discussed in the current literature. Different detectors with or without corrections are recommended. Correction factors are often derived by Monte Carlo methods, where the bias due to approximations in the model is difficult to judge. Over that, results appear to be contradictory in some cases. In this work, output factors were measured for field sizes from 4 mm up to 180 mm side length with different detectors. A simple linear correction for the energy response of solid state detectors is proposed. This led to identical values down to 8 mm field size, as long as the size of the detector is small against the field size. The correction was of the order of a few percent. For a shielded silicon diode it was well below 1%. A physically meaningful function is proposed in order to calculate output factors for arbitrary field sizes with high accuracy.

Precision of image-guided radiotherapy (IGRT) in six degrees of freedom and limitations in clinical practice.

Purpose:To evaluate the precision of image-guided radiotherapy (IGRT) using cone-beam computed tomography (CB-CT) for volume imaging and a robotic couch for correcting setup errors in six degrees of freedom.Patients and Methods:47 consecutive patients with 372 fractions were classified according to whether a patient fixation device was used (patfix: n = 28) or not (patnon-fix: n = 19). Prior to treatment a CB-CT was acquired and translational and rotational setup errors were corrected online without an action level using a robotic couch (HexaPOD). A second CB-CT was acquired after the correction process and after treatment in 134 and 238 fractions, respectively.Results:In 17 fractions (4.6%) rotational errors > 3° exceeded the motion range of the HexaPOD. Errors (3D vector) after the correction process were significantly smaller for patfix compared to patnon-fix (p < 0.001): 0.9 mm ± 0.5 mm and 1.6 mm ± 0.8 mm, respectively. For patnon-fix the correction of rotational errors resulted in displacements of the patients on the angled couch of 0.6 mm/1°. Intrafractional motion further decreased precision in patnon-fix but not in patfix.Conclusion:Very high precision in cranial and extracranial treatment of immobilized patients was demonstrated. Without application of adequate immobilization the correction of rotational errors and intrafractional patient motion significantly decreased the accuracy of the online correction protocol.Ziel:Untersucht wurde die Präzision eines bildgestützten Bestrahlungsprotokolls, basierend auf Volumenbildgebung mittels Cone-Beam-Computertomographie (CB-CT) und Korrektur von Lagerungsfehlern in sechs Freiheitsgraden.Patienten und Methodik:47 Patienten mit 372 Behandlungsfraktionen wurden ausgewertet: Differenziert wurde zwischen Patienten, die auf dem Behandlungstisch fixiert wurden (patfix: n = 28) oder nicht (patnon-fix: n = 19). Vor der Behandlung wurde ein CB-CT angefertigt, und translatorische und rotatorische Lagerungsfehler wurden vollständig mittels eines robotischen Behandlungstisches (HexaPOD) korrigiert. Bildgebung nach der Fehlerkorrektur und nach der Behandlung wurde in jeweils 134 und 238 Fraktionen durchgeführt.Ergebnisse:Bei 17 Fraktionen (4,6%) überschritten die Rotationsfehler die Reichweite des HexaPOD von 3°. Fehler nach der Korrektur (3D-Vektor) waren bei patnon-fix im Vergleich zu patfix signifikant größer (p < 0,001): 1,6 mm ± 0,8 mm versus 0,9 mm ± 0,5 mm. Bei patnon-fix führte die Korrektur von Rotationsfehlern zu einer Verlagerung der Patienten auf dem abgewinkelten HexaPOD von 0,6 mm/1°. Intrafraktionelle Patientenbewegung resultierte in weiteren Fehlern bei patnon-fix, jedoch nicht bei patfix.Schlussfolgerung:Bei Immobilisierung der Patienten wurde eine Präzision mittels bildgestützter Radiotherapie von 1 mm und 1° erreicht. Ohne ausreichende Immobilisation reduzieren Verlagerungen nach Korrektur von Rotationsfehlern und intrafraktionelle Patientenbewegungen den Nutzen eines solches Behandlungsprotokolls erheblich.

A Collaborative Analysis of Stereotactic Lung Radiotherapy Outcomes for Early-Stage Non–Small-Cell Lung Cancer Using Daily Online Cone-Beam Computed Tomography Image-Guided Radiotherapy

Introduction: We report lung stereotactic-body radiotherapy (SBRT) outcomes for a large pooled cohort treated using daily online cone-beam computed tomography. Methods: Five hundred and five stage I–IIB (T1-3N0M0) non–small-cell lung cancer (NSCLC) cases underwent SBRT using cone-beam computed tomography image guidance at five international institutions from 1998 to 2010. Median age was 74 years (range, 42–92) whereas median forced expiratory volume in 1 second/diffusing lung capacity for carbon monoxide were 1.4 liter (65%) and 10.8 ml/min/mmHg (53%). Of the 505 cases, 64% were biopsy proven and 87% medically inoperable. Staging was: IA 63%, IB 33%, IIA 2%, and recurrent 1%. Median max tumor dimension was 2.6 cm (range, 0.9–8.5). Median heterogeneously calculated volumetric prescription dose (PD) was 54 Gy (range, 20–64 Gy) in three fractions (range, 1–15) over 8 days (range, 1–27). Median biologically equivalent PD biological equivalent doses (BED10) was 132 Gy (range, 60–180). Results: With a median follow-up of 1.6 years (range, 0.1–7.3), the 2-year Kaplan–Meier local control (LC), regional control, and distant metastasis (DM) rates were 94%, 89%, and 20%, respectively, whereas cause-specific and overall survival were 87% and 60% (78% operable, 58% inoperable, p = 0.01), respectively. Stage, gross-tumor volume size (≥ 2.7 cm) and PD(BED10) predicted local relapse (LR) and DM. LR was 15% for BED10 less than 105 Gy versus 4% for BED10 of 105 Gy or more (p < 0.001); DM was 31% versus 18% for BED10 less than 105 versus 105 Gy or more (p = 0.01). On multivariate analysis, PD(BED10) and elapsed days during radiotherapy predicted LR; gross-tumor volume size predicted DM. Grade 2 or higher pneumonitis, rib fracture, myositis, and dermatitis were 7%, 3%, 1%, and 2%, respectively. Conclusions: In the largest early-stage NSCLC SBRT data set to date, a high rate of local control was achieved, which was correlated with a PD(BED10) of 105 Gy or more. Failures were primarily distant, severe toxicities were rare, and overall survival was encouraging in operable patients.

Potential of image-guidance, gating and real-time tracking to improve accuracy in pulmonary stereotactic body radiotherapy

PURPOSE To evaluate the potential of image-guidance, gating and real-time tumor tracking to improve accuracy in pulmonary stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS Safety margins for compensation of inter- and intra-fractional uncertainties of the target position were calculated based on SBRT treatments of 43 patients with pre- and post-treatment cone-beam CT imaging. Safety margins for compensation of breathing motion were evaluated for 17 pulmonary tumors using respiratory correlated CT, model-based segmentation of 4D-CT images and voxel-based dose accumulation; the target in the mid-ventilation position was the reference. RESULTS Because of large inter-fractional base-line shifts of the tumor, stereotactic patient positioning and image-guidance based on the bony anatomy required safety margins of 12 mm and 9 mm, respectively. Four-dimensional image-guidance targeting the tumor itself and intra-fractional tumor tracking reduced margins to <5 mm and <3 mm, respectively. Additional safety margins are required to compensate for breathing motion. A quadratic relationship between tumor motion and margins for motion compensation was observed: safety margins of 2.4mm and 6mm were calculated for compensation of 10 mm and 20 mm motion amplitudes in cranio-caudal direction, respectively. CONCLUSION Four-dimensional image-guidance with pre-treatment verification of the target position and online correction of errors reduced safety margins most effectively in pulmonary SBRT.

Cone-beam CT based image-guidance for extracranial stereotactic radiotherapy of intrapulmonary tumors

Cone-beam CT (CB-CT) based image-guidance was evaluated for extracranial stereotactic radiotherapy of intrapulmonary tumors. A total of 21 patients (25 lesions: prim. NSCLC n = 6; pulmonary metastases n = 19) were treated with stereotactic radiotherapy (1 to 8 fractions). Prior to every fraction a CB-CT was acquired in treatment position, errors between planned and actual tumor position were measured and corrected. Intra- and inter-observer variability of manual evaluation of tumor position error was investigated and this manual method was compared with automatic image registration. Based on CB-CTs from 66 fractions the discrepancy (3-D vector) between planned and actual tumor position was 7.7 mm ±1.3 mm. Tumor position error relative to the bony anatomy was 5.3 mm ±1.2 mm, the correlation between bony anatomy and tumor position was poor. Intra-observer and inter-observer variability of manual evaluation of tumor position error was 0.9 mm ±0.8 mm and 2.3 mm ±1.1 mm, respectively. Automatic image registration showed highly reproducible results (<1 mm). However, compared with manual registration a systematic error was found in direction of predominant tumor breathing motion (2.5 mm vs 1.4 mm). Image-guidance using CB-CT was validated for high precision radiotherapy of intrapulmonary tumors. It was shown that both the planning reference and the verification image study have to consider tumor breathing motion.

Dose–response relationship for radiation-induced pneumonitis after pulmonary stereotactic body radiotherapy

PURPOSE To evaluate dosimetric factors predictive for radiation-induced pneumonitis (RP) after pulmonary stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS A retrospective analysis was performed based on 59 consecutive patients treated with cone-beam CT-based image-guided SBRT for primary NSCLC (n=21) or pulmonary metastases (n=54). The majority of patients were treated with radiosurgery of 26 Gy to 80% (n=29) or three fractions of 12.5 Gy to 65% (n=40). To correct for different single fraction doses, local doses were converted to 2 Gy equivalent normalized total doses (NTDs) using α/β ratio of 3 Gy for RP. Dose-volume parameters and incidences of RP ≥ grade II SWOG were fitted using NTCP models. RESULTS Eleven patients developed RP grade II. With an average MLD of 10.3±5.6 Gy to the ipsilateral lung, a significant dose-response relationship was observed: the MLD was 12.5±4.3 Gy and 9.9±5.8 Gy for patients with and without development of RP, respectively. Additionally, volumes of the lung exposed to minimum doses between 2.5 and 50 Gy (V(2.5)-V(50)) were correlated with incidences of RP with a continuous decrease of the goodness of fit for higher doses. CONCLUSIONS The MLD and V(2.5)-V(50) of the ipsilateral lung were correlated with incidences of RP after pulmonary SBRT.

Potential of Adaptive Radiotherapy to Escalate the Radiation Dose in Combined Radiochemotherapy for Locally Advanced Non–Small Cell Lung Cancer

PURPOSE To evaluate the potential of adaptive radiotherapy (ART) for advanced-stage non-small cell lung cancer (NSCLC) in terms of lung sparing and dose escalation. METHODS AND MATERIALS In 13 patients with locally advanced NSCLC, weekly CT images were acquired during radio- (n=1) or radiochemotherapy (n=12) for simulation of ART. Three-dimensional (3D) conformal treatment plans were generated: conventionally fractionated doses of 66 Gy were prescribed to the planning target volume without elective lymph node irradiation (Plan_3D). Using a surface-based algorithm of deformable image registration, accumulated doses were calculated in the CT images acquired during the treatment course (Plan_4D). Field sizes were adapted to tumor shrinkage once in week 3 or 5 and twice in weeks 3 and 5. RESULTS A continuous tumor regression of 1.2% per day resulted in a residual gross tumor volume (GTV) of 49%±15% after six weeks of treatment. No systematic differences between Plan_3D and Plan_4D were observed regarding doses to the GTV, lung, and spinal cord. Plan adaptation to tumor shrinkage resulted in significantly decreased lung doses without compromising GTV coverage: single-plan adaptation in Week 3 or 5 and twice-plan adaptation in Weeks 3 and 5 reduced the mean lung dose by 5.0%±4.4%, 5.6%±2.9% and 7.9%±4.8%, respectively. This lung sparing with twice ART allowed an iso-mean lung dose escalation of the GTV dose from 66.8 Gy±0.8 Gy to 73.6 Gy±3.8 Gy. CONCLUSIONS Adaptation of radiotherapy to continuous tumor shrinkage during the treatment course reduced doses to the lung, allowed significant dose escalation and has the potential of increased local control.

Is there a lower limit of pretreatment pulmonary function for safe and effective stereotactic body radiotherapy for early-stage non-small cell lung cancer?

Introduction: To evaluate the influence of pretreatment pulmonary function (PF) on survival, early and late pulmonary toxicity after stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer. Methods: Four hundred eighty-three patients with 505 tumors of early-stage non-small cell lung cancer cT1–3 cN0 were treated with image-guided SBRT at five international institutions (1998–2010). Sixty-four percent of the tumors were biopsy-proven and 18F-fluorodeoxyglucose-positron emission tomography was performed for staging in 84%. Image-guided SBRT was performed with a median of three fractions to a median total dose of 54 Gy. Pretreatment PF was available for 423 patients, and 617 posttreatment PF tests from 270 patients were available. Results: A large variability of pretreatment PF was observed: the 90% range of forced expiratory volume in 1 second and diffusing capacity for carbon monoxide was 29 to 109% and 5.5 to 19.1 ml/min/mmHg, respectively. PF was significantly correlated with overall survival but not cause-specific survival: diffusing capacity for carbon monoxide of 11.2 ml/min/mmHg differentiated between 3-year overall survival of 66% and 42%. Radiation-induced pneumonitis grade ≥II occurred in 7% of patients and was not increased in patients with lower PF. A significant and progressive change of PF was observed after SBRT: PF decreased by 3.6% and 6.8% on average within 6 and 6 to 24 months after SBRT, respectively. Changes of PF after SBRT were significantly correlated with pretreatment PF: PF improved for worst pretreatment PF and the largest loss was observed for best pretreatment PF. Conclusions: Image-guided SBRT is safe in terms of acute and chronic pulmonary toxicity even for patients with severe pulmonary comorbidities. SBRT should be considered as a curative treatment option for inoperable patients with pretreatment PF as reported in this study.