Transcutaneous Vagal Nerve Stimulation Alone or in Combination With Radiotherapy Stimulates Lung Tumor Infiltrating Lymphocytes But Fails to Suppress Tumor Growth.

The combination of radiotherapy (RT) with immunotherapy represents a promising treatment modality for non-small cell lung cancer (NSCLC) patients. As only a minority of patients shows a persistent response today, a spacious optimization window remains to be explored. Previously we showed that fractionated RT can induce a local immunosuppressive profile. Based on the evolving concept of an immunomodulatory role for vagal nerve stimulation (VNS), we tested its therapeutic and immunological effects alone and in combination with fractionated RT in a preclinical-translational study. Lewis lung carcinoma-bearing C57Bl/6 mice were treated with VNS, fractionated RT or the combination while a patient cohort with locally advanced NSCLC receiving concurrent radiochemotherapy (ccRTCT) was enrolled in a clinical trial to receive either sham or effective VNS daily during their 6 weeks of ccRTCT treatment. Preclinically, VNS alone or with RT showed no therapeutic effect yet VNS alone significantly enhanced the activation profile of intratumoral CD8+ T cells by upregulating their IFN-γ and CD137 expression. In the periphery, VNS reduced the RT-mediated rise of splenic, but not blood-derived, regulatory T cells (Treg) and monocytes. In accordance, the serological levels of protumoral CXCL5 next to two Treg-attracting chemokines CCL1 and CCL22 were reduced upon VNS monotherapy. In line with our preclinical findings on the lack of immunological changes in blood circulating immune cells upon VNS, immune monitoring of the peripheral blood of VNS treated NSCLC patients (n=7) did not show any significant changes compared to ccRTCT alone. As our preclinical data do suggest that VNS intensifies the stimulatory profile of the tumor infiltrated CD8+ T cells, this favors further research into non-invasive VNS to optimize current response rates to RT-immunotherapy in lung cancer patients.

The METABANK score: A clinical tool to predict survival after stereotactic radiotherapy for oligometastatic disease.

BACKGROUND AND PURPOSE: Stereotactic radiotherapy (SRT, SBRT) is widely used in oligometastatic cancer, but the heterogeneity of the population complicates estimation of the prognosis. We investigated the role of different clinical and inflammatory parameters. MATERIALS AND METHODS: We included all patients treated with SRT for 1-5 oligometastases between 2003 and 2017 in our center. Patients were randomized between a model training set (2/3) and a separate validation set (1/3). A Cox regression model was built, validated and risk points were attributed to the resulting parameters. RESULTS: 403 patients received SRT for 760 metastases. Treated sites were mainly lung, liver, nodal areas, and brain. Most common primaries were colorectal and lung cancer. Median follow-up for living patients reached 42 months and median overall survival (MS) was 26.6 months (95% CI 23.8-29.3). Five independent adverse factors were discriminated: male sex, synchronous timing of oligometastases, brain metastasis, non-adenocarcinoma histology, KPS <80. A risk score is formed by summation of the points of each factor (M:4, T:2, B:7, N:7, K:8). Four risk groups were defined: (1) 0-2 points: MS 41.2 months (95% CI 30.2-52.3); (2) 3-8 points: 29.3 months (24.6-34.0); (3) 9-13 points: 17.4 months (10.1-24.7), and (4) 14-28 points: 7.9 months (5.5-10.3). CONCLUSION: We propose a prognostic score applicable in a variety of primary tumors and disease locations, including presence of brain metastases. The nomogram and risk groups can be used to stratify patients in new trials and to support individualized care for oligometastatic patients. An online calculator will become available at predictcancer.org.

The long- and short-term variability of breathing induced tumor motion in lung and liver over the course of a radiotherapy treatment.

PURPOSE: To evaluate the short and long-term variability of breathing induced tumor motion. MATERIALS AND METHODS: 3D tumor motion of 19 lung and 18 liver lesions captured over the course of an SBRT treatment were evaluated and compared to the motion on 4D-CT. An implanted fiducial could be used for unambiguous motion information. Fast orthogonal fluoroscopy (FF) sequences, included in the treatment workflow, were used to evaluate motion during treatment. Several motion parameters were compared between different FF sequences from the same fraction to evaluate the intrafraction variability. To assess interfraction variability, amplitude and hysteresis were compared between fractions and with the 3D tumor motion registered by 4D-CT. Population based margins, necessary on top of the ITV to capture all motion variability, were calculated based on the motion captured during treatment. RESULTS: Baseline drift in the cranio-caudal (CC) or anterior-poster (AP) direction is significant (ie. >5 mm) for a large group of patients, in contrary to intrafraction amplitude and hysteresis variability. However, a correlation between intrafraction amplitude variability and mean motion amplitude was found (Pearson's correlation coefficient, r = 0.72, p < 10-4). Interfraction variability in amplitude is significant for 46% of all lesions. As such, 4D-CT accurately captures the motion during treatment for some fractions but not for all. Accounting for motion variability during treatment increases the PTV margins in all directions, most significantly in CC from 5 mm to 13.7 mm for lung and 8.0 mm for liver. CONCLUSION: Both short-term and day-to-day tumor motion variability can be significant, especially for lesions moving with amplitudes above 7 mm. Abandoning passive motion management strategies in favor of more active ones is advised.

Treating patients with Dynamic Wave Arc: First clinical experience.

BACKGROUND AND PURPOSE: Dynamic Wave Arc (DWA) is a system-specific noncoplanar arc technique that combines synchronized gantry-ring rotation with D-MLC optimization. This paper presents the clinical workflow, quality assurance program, and reports the geometric and dosimetric results of the first patient cohort treated with DWA. METHODS AND MATERIALS: The RayStation TPS was clinically integrated on the Vero SBRT platform for DWA treatments. The first 15 patients treated with DWA represent a broad range of treatment sites: breast boost, prostate, lung SBRT and bone metastases, which allowed us to explore the potentials and assess the limitations of the current DWA site-specific template solution. For the DWA verification a variety of QA equipment was used, from 3D diode array to an anthropomorphic end-to-end phantom. The geometric accuracy of each arc was verified with an independent orthogonal fluoroscopy method. RESULTS: The average beam-on delivery time was 3min, ranging from 1.22min to 8.82min. All patient QAs passed our institutional clinical criteria of gamma index. For both EBT3 film and Delta4 measurements, DWA planned versus delivered dose distributions presented an average agreement above 97%. An overall mean gantry-ring geometric deviation of -0.03°±0.46° and 0.18°±0.26° was obtained, respectively. CONCLUSION: For the first time, DWA has been translated into the clinic and used to treat various treatment sides. DWA has been successfully added to the noncoplanar rotational IMRT techniques arsenal, allowing additional flexibility in dose shaping while preserving dosimetrically robust delivery.

Initial characterization, dosimetric benchmark and performance validation of Dynamic Wave Arc.

BACKGROUND: Dynamic Wave Arc (DWA) is a clinical approach designed to maximize the versatility of Vero SBRT system by synchronizing the gantry-ring noncoplanar movement with D-MLC optimization. The purpose of this study was to verify the delivery accuracy of DWA approach and to evaluate the potential dosimetric benefits. METHODS: DWA is an extended form of VMAT with a continuous varying ring position. The main difference in the optimization modules of VMAT and DWA is during the angular spacing, where the DWA algorithm does not consider the gantry spacing, but only the Euclidian norm of the ring and gantry angle. A preclinical version of RayStation v4.6 (RaySearch Laboratories, Sweden) was used to create patient specific wave arc trajectories for 31 patients with various anatomical tumor regions (prostate, oligometatstatic cases, centrally-located non-small cell lung cancer (NSCLC) and locally advanced pancreatic cancer-LAPC). DWA was benchmarked against the current clinical approaches and coplanar VMAT. Each plan was evaluated with regards to dose distribution, modulation complexity (MCS), monitor units and treatment time efficiency. The delivery accuracy was evaluated using a 2D diode array that takes in consideration the multi-dimensionality of DWA during dose reconstruction. RESULTS: In centrally-located NSCLC cases, DWA improved the low dose spillage with 20 %, while the target coverage was increased with 17 % compared to 3D CRT. The structures that significantly benefited from using DWA were proximal bronchus and esophagus, with the maximal dose being reduced by 17 % and 24 %, respectively. For prostate and LAPC, neither technique seemed clearly superior to the other; however, DWA reduced with more than 65 % of the delivery time over IMRT. A steeper dose gradient outside the target was observed for all treatment sites (p < 0.01) with DWA. Except the oligometastatic cases, where the DWA-MCSs indicate a higher modulation, both DWA and VMAT modalities provide plans of similar complexity. The average É£ (3 % /3 mm) passing rate for DWA plans was 99.2 ± 1 % (range from 96.8 to 100 %). CONCLUSIONS: DWA proven to be a fully functional treatment technique, allowing additional flexibility in dose shaping, while preserving dosimetrically robust delivery and treatment times comparable with coplanar VMAT.

Motion management during SBRT for oligometastatic cancer: Results of a prospective phase II trial.

PURPOSE: To optimize the local control of stereotactic body radiotherapy (SBRT) using the Vero-SBRT system and respiratory motion management in patients with oligometastatic cancer. MATERIALS AND METHODS: Patients with five or less metastases were eligible. In metastases with significant motion, a fiducial was implanted for Vero dynamic tracking. For other metastases an internal target volume (ITV) was defined to encompass the respiratory tumor trajectory. A dose of 50Gy in 10 fractions was prescribed on the 80% isodose line. RESULTS: We treated 87 metastases in 44 patients, with colorectal cancer as the most common primary origin (65.9%). Metastatic sites were mainly lung (n=62) and liver (n=17). Twenty-seven metastases were treated with dynamic tracking, the remaining 60 using the ITV-concept. Three patients (7%) experienced grade ⩾3 toxicity. After a median follow-up of 12months, the overall one-year local control (LC) amounted to 89% (95% CI 77-95%), with corresponding values of 90% and 88% for the metastases irradiated with the ITV-approach and dynamic tracking, respectively. Median progression-free survival reached 6.5months, one-year overall survival 95%. CONCLUSIONS: SBRT with proper respiratory motion management resulted in a high LC and an acceptable toxicity profile in oligometastatic cancer patients.

Dynamic Lung Tumor Tracking for Stereotactic Ablative Body Radiation Therapy.

Physicians considering stereotactic ablative body radiation therapy (SBRT) for the treatment of extracranial cancer targets must be aware of the sizeable risks for normal tissue injury and the hazards of physical tumor miss. A first-of-its-kind SBRT platform achieves high-precision ablative radiation treatment through a combination of versatile real-time imaging solutions and sophisticated tumor tracking capabilities. It uses dual-diagnostic kV x-ray units for stereoscopic open-loop feedback of cancer target intrafraction movement occurring as a consequence of respiratory motions and heartbeat. Image-guided feedback drives a gimbaled radiation accelerator (maximum 15 x 15 cm field size) capable of real-time ±4 cm pan-and-tilt action. Robot-driven ±60° pivots of an integrated ±185° rotational gantry allow for coplanar and non-coplanar accelerator beam set-up angles, ultimately permitting unique treatment degrees of freedom. State-of-the-art software aids real-time six dimensional positioning, ensuring irradiation of cancer targets with sub-millimeter accuracy (0.4 mm at isocenter). Use of these features enables treating physicians to steer radiation dose to cancer tumor targets while simultaneously reducing radiation dose to normal tissues. By adding respiration correlated computed tomography (CT) and 2-[(18)F] fluoro-2-deoxy-ᴅ-glucose ((18)F-FDG) positron emission tomography (PET) images into the planning system for enhanced tumor target contouring, the likelihood of physical tumor miss becomes substantially less. In this article, we describe new radiation plans for the treatment of moving lung tumors.

Feasibility of markerless tumor tracking by sequential dual-energy fluoroscopy on a clinical tumor tracking system.

A novel approach to dual-energy imaging for markerless tumor tracking was proposed consisting of sequential dual-energy fluoroscopy, omitting the need for fast-switching kV generators. The implementation of this approach on a clinical tumor tracking system and its efficacy is shown feasible through optimization of the imaging parameters.

A multi-centre analysis of treatment procedures and error components in dynamic tumour tracking radiotherapy.

PURPOSE: This study aimed to compare procedures for dynamic tumour tracking (DTT) using a gimbal-mounted linac between centres in Japan (KU-IBRI) and Belgium (UZB), to quantify tracking error (TE), and to estimate tumour-fiducial uncertainties and PTV margins. METHODS: Twenty-two patients were evaluated. TE was divided into components originating from the patient, fraction, segment, and residuals. RESULTS: KU-IBRI applied DTT to lung cancer, while UZB treated both the lung and liver. Patients from UZB were younger and had a higher body mass index. DTT procedures differed in the use of body fixation, correction for set-up error, type of fiducial markers, and goodness of fit of correlation model. TE was larger at UZB in the intra-fraction components, whereas the tumour-fiducial uncertainties were estimated to be larger at KU-IBRI. These results ultimately led to similar PTV margins at both centres (2.1, 4.2, and 2.6 mm for KU-IBRI; 2.4, 3.6, and 2.0 mm for UZB in LR, AP, and SI, respectively, for 99% coverage of patients). CONCLUSION: Several differences in procedures and patient characteristics were observed that affected TE and tumour-fiducial uncertainties. This analysis confirmed similar accuracy in DTT delivery and adequate PTV margins in the different centres based on their local specific workflows.

Improving the intra-fraction update efficiency of a correlation model used for internal motion estimation during real-time tumor tracking for SBRT patients: fast update or no update?

BACKGROUND AND PURPOSE: For tumor tracking, a correlation model is used to estimate internal tumor position based on external surrogate motion. When patients experience an internal/external surrogate drift, an update of the correlation model is required to continue tumor tracking. In this study, the accuracy of the internal tumor position estimation for both the clinical available update at discrete points in time (rebuild) and an in-house developed non-clinical online update approach was investigated. METHODS: A dynamic phantom with superimposed baseline drifts and 14 SBRT patients, treated with real-time tumor tracking (RTTT) on the Vero system, were retrospectively simulated for three update scenarios, respectively no update, clinical rebuild and 0.5 Hz automated online update of the correlation model. By comparing the target positions based on 0.5 Hz verification X-ray images with the estimated internal tumor positions regarding all three update scenarios, 95th percentile modeling errors (ME95), incidences of full geometrical coverage of the CTV by a 5 mm extended PTV (P5mm) and population-based PTV margins were calculated. Further, the treatment time reduction was estimated when switching from the clinical rebuild approach to the online correlation model update. RESULTS: For dynamic phantom motion with baseline drifts up to 0.4 mm/min, a 0.5 Hz intra-fraction update showed a similar accuracy in terms of ME95 and P5 mm compared to clinical rebuild. For SBRT patients treated on Vero with RTTT, accuracy was improved by 0.5 Hz online update compared to the clinical rebuild protocol, yielding smaller PTV margins (from 3.2 mm to 2.7 mm), reduced ME95,3D (from 4.1 mm to 3.4 mm) and an increased 5th percentile P5 mm (from 90.7% to 96.1%) for the entire patient group. Further, 80% of treatment sessions were reduced in time with on average 5.5 ± 4.1(1 SD)min. CONCLUSION: With a fast (0.5 Hz) automated online update of the correlation model, an efficient RTTT workflow with improved geometrical accuracy was obtained.

Treating patients with real-time tumor tracking using the Vero gimbaled linac system: implementation and first review.

PURPOSE: To report on the first clinical application of a real-time tumor tracking (RTTT) solution based on the Vero SBRT gimbaled linac system for treatment of moving tumors. METHODS AND MATERIALS: A first group of 10 SBRT patients diagnosed with NSCLC or oligometastatic disease in lung or liver was treated with the RTTT technique. The PTV volumes and OAR exposure were benchmarked against the widely used ITV approach. Based on data acquired during execution of RTTT treatments, a first review was performed of the process. RESULTS: The 35% PTV volume reduction with RTTT of the studied single lesions SBRT irradiations of small target volumes is expected to result in a small (<1%) reduction of lung or liver NTCP. A GTV-PTV margin of 5.0mm was applied for treatment planning of RTTT. From patient data on residual geometric uncertainties, a CTV-PTV margin of 3.2mm was calculated. Reduction of the GTV-PTV margin below 5.0mm without better understanding of biological definition of tumor boundaries was discouraged. Total treatment times were reduced to 34.4 min on average. CONCLUSION: A considerable PTV volume reduction was achieved applying RTTT and time efficiency for respiratory correlated SBRT was reestablished with Vero RTTT.

Dosimetric comparison of different treatment modalities for stereotactic radiosurgery of arteriovenous malformations and acoustic neuromas.

PURPOSE: We investigated the influence of beam modulation on treatment planning by comparing four available stereotactic radiosurgery (SRS) modalities: Gamma-Knife-Perfexion, Novalis-Tx Dynamic-Conformal-Arc (DCA) and Dynamic-Multileaf-Collimation-Intensity-Modulated-radiotherapy (DMLC-IMRT), and Cyberknife. MATERIAL AND METHODS: Patients with arteriovenous malformation (n = 10) or acoustic neuromas (n = 5) were planned with different treatment modalities. Paddick conformity index (CI), dose heterogeneity (DH), gradient index (GI) and beam-on time were used as dosimetric indices. RESULTS: Gamma-Knife-Perfexion can achieve high degree of conformity (CI = 0.77 ± 0.04) with limited low-doses (GI = 2.59 ± 0.10) surrounding the inhomogeneous dose distribution (D(H) = 0.84 ± 0.05) at the cost of treatment time (68.1 min ± 27.5). Novalis-Tx-DCA improved this inhomogeneity (D(H) = 0.30 ± 0.03) and treatment time (16.8 min ± 2.2) at the cost of conformity (CI = 0.66 ± 0.04) and Novalis-TX-DMLC-IMRT improved the DCA CI (CI = 0.68 ± 0.04) and inhomogeneity (D(H) = 0.18 ± 0.05) at the cost of low-doses (GI = 3.94 ± 0.92) and treatment time (21.7 min ± 3.4) (p<0.01). Cyberknife achieved comparable conformity (CI = 0.77 ± 0.06) at the cost of low-doses (GI = 3.48 ± 0.47) surrounding the homogeneous (D(H) = 0.22 ± 0.02) dose distribution and treatment time (28.4min±8.1) (p<0.01). CONCLUSIONS: Gamma-Knife-Perfexion will comply with all SRS constraints (high conformity while minimizing low-dose spread). Multiple focal entries (Gamma-Knife-Perfexion and Cyberknife) will achieve better conformity than High-Definition-MLC of Novalis-Tx at the cost of treatment time. Non-isocentric beams (Cyberknife) or IMRT-beams (Novalis-Tx-DMLC-IMRT) will spread more low-dose than multiple isocenters (Gamma-Knife-Perfexion) or dynamic arcs (Novalis-Tx-DCA). Inverse planning and modulated fluences (Novalis-Tx-DMLC-IMRT and CyberKnife) will deliver the most homogeneous treatment. Furthermore, Linac-based systems (Novalis and Cyberknife) can perform image verification at the time of treatment delivery.

A complementary dual-modality verification for tumor tracking on a gimbaled linac system.

BACKGROUND AND PURPOSE: For dynamic tracking of moving tumors, robust intra-fraction verification was required, to assure that tumor motion was properly managed during the course of radiotherapy. A dual-modality verification system, consisting of an on-board orthogonal kV and planar MV imaging device, was validated and applied retrospectively to patient data. METHODS AND MATERIALS: Real-time tumor tracking (RTTT) was managed by applying PAN and TILT angular corrections to the therapeutic beam using a gimbaled linac. In this study, orthogonal X-ray imaging and MV EPID fluoroscopy was acquired simultaneously. The tracking beam position was derived from respectively real-time gimbals log files and the detected field outline on EPID. For both imaging modalities, the moving target was localized by detection of an implanted fiducial. The dual-modality tracking verification was validated against a high-precision optical camera in phantom experiments and applied to clinical tracking data from a liver and two lung cancer patients. RESULTS: Both verification modalities showed a high accuracy (<0.3mm) during validation on phantom. Marker detection on EPID was influenced by low image contrast. For the clinical cases, gimbaled tracking showed a 90th percentile error (E90) of 3.45 (liver), 2.44 (lung A) and 3.40 mm (lung B) based on EPID fluoroscopy and good agreement with XR-log file data by an E90 of 3.13, 1.92 and 3.33 mm, respectively, during beam on. CONCLUSION: Dual-modality verification was successfully implemented, offering the possibility of detailed reporting on RTTT performance.

Initial assessment of tumor tracking with a gimbaled linac system in clinical circumstances: a patient simulation study.

PURPOSE: To have an initial assessment of the Vero Dynamic Tracking workflow in clinical circumstances and quantify the performance of the tracking system, a simulation study was set up on 5 lung and liver patients. METHODS AND MATERIALS: The preparatory steps of a tumor tracking treatment, based on fiducial markers implanted in the tumor, were executed allowing pursuit of the tumor with the gimbaled linac and monitoring X-rays acquisition, however, without activating the 6 MV beam. Data were acquired on workflow time-efficiency, tracking accuracy and imaging exposure. RESULTS: The average time between the patient entering the treatment room and the first treatment field was about 9 min. The time for building the correlation model was 3.2 min. Tracking errors of 0.55 and 0.95 mm (1σ) were observed in PAN/TILT direction and a 2D range of 3.08 mm. A skin dose was determined of 0.08 mGy/image, with a source-to-skin distance of 900 mm and kV exposure of 1 mAs. On average 1.8 mGy/min kV skin dose was observed for 1 Hz monitoring. CONCLUSION: The Vero tracking solution proved to be fully functional and showed performance comparable with other real-time tracking systems.

Setup accuracy of the Novalis ExacTrac 6DOF system for frameless radiosurgery.

PURPOSE: Stereotactic radiosurgery using frame-based positioning is a well-established technique for the treatment of benign and malignant lesions. By contrast, a new trend toward frameless systems using image-guided positioning techniques is gaining mainstream acceptance. This study was designed to measure the detection and positioning accuracy of the ExacTrac/Novalis Body (ET/NB) for rotations and to compare the accuracy of the frameless with the frame-based radiosurgery technique. METHODS AND MATERIALS: A program was developed in house to rotate reference computed tomography images. The angles measured by the system were compared with the known rotations. The accuracy of ET/NB was evaluated with a head phantom with seven lead beads inserted, mounted on a treatment couch equipped with a robotic tilt module, and was measured with a digital water level and portal films. Multiple hidden target tests (HTT) were performed to measure the overall accuracy of the different positioning techniques for radiosurgery (i.e., frameless and frame-based with relocatable mask or invasive ring, respectively). RESULTS: The ET/NB system can detect rotational setup errors with an average accuracy of 0.09° (standard deviation [SD] 0.06°), 0.02° (SD 0.07°), and 0.06° (SD 0.14°) for longitudinal, lateral, and vertical rotations, respectively. The average positioning accuracy was 0.06° (SD 0.04°), 0.08° (SD 0.06°), and 0.08° (SD 0.07°) for longitudinal, lateral and vertical rotations, respectively. The results of the HTT showed an overall three-dimensional accuracy of 0.76 mm (SD 0.46 mm) for the frameless technique, 0.87 mm (SD 0.44 mm) for the relocatable mask, and 1.19 mm (SD 0.45 mm) for the frame-based technique. CONCLUSIONS: The study showed high detection accuracy and a subdegree positioning accuracy. On the basis of phantom studies, the frameless technique showed comparable accuracy to the frame-based approach.

Single fraction versus fractionated linac-based stereotactic radiotherapy for vestibular schwannoma: a single-institution experience.

PURPOSE: To evaluate and compare outcomes for patients with vestibular schwannoma (VS) treated in a single institution with linac-based stereotactic radiosurgery (SRS) or by fractionated stereotactic radiotherapy (SRT). METHODS AND MATERIALS: One hundred and nineteen patients (SRS = 78, SRT = 41) were treated. For both SRS and SRT, beam shaping is performed by a mini-multileaf collimator. For SRS, a median single dose of 12.5 Gy (range, 11-14 Gy), prescribed to the 80% isodose line encompassing the target, was applied. Of the 42 SRT treatments, 32 treatments consisted of 10 fractions of 3-4 Gy, and 10 patients received 25 sessions of 2 Gy, prescribed to the 100% with the 95% isodose line encompassing the planning target volume. Mean largest tumor diameter was 16.6 mm in the SRS and 24.6 mm in the SRT group. Local tumor control, cranial nerve toxicity, and preservation of useful hearing were recorded. Any new treatment-induced cranial nerve neuropathy was scored as a complication. RESULTS: Median follow-up was 62 months (range, 6-136 months), 5 patients progressed, resulting in an overall 5-year local tumor control of 95%. The overall 5-year facial nerve preservation probability was 88% and facial nerve neuropathy was statistically significantly higher after SRS, after prior surgery, for larger tumors, and in Koos Grade ≥3. The overall 5-year trigeminal nerve preservation probability was 96%, not significantly influenced by any of the risk factors. The overall 4-year probability of preservation of useful hearing (Gardner-Robertson score 1 or 2) was 68%, not significantly different between SRS or SRT (59% vs. 82%, p = 0.089, log rank). CONCLUSION: Linac-based RT results in good local control and acceptable clinical outcome in small to medium-sized vestibular schwannomas (VSs). Radiosurgery for large VSs (Koos Grade ≥3) remains a challenge because of increased facial nerve neuropathy.

Prospective, risk-adapted strategy of stereotactic body radiotherapy for early-stage non-small-cell lung cancer: results of a Phase II trial.

PURPOSE: Validation of a prospective, risk-adapted strategy for early-stage non-small-cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS: Patients with a T1-3N0M0 (American Joint Committee on Cancer 6th edition) NSCLC were accrued. Using the Radiation Therapy Oncology Group definition, patients were treated to a total dose of 60,Gy in three fractions for peripherally located lesions and four fractions for centrally located lesions. The primary endpoint was toxicity, graded according to the Radiation Therapy Oncology Group acute and late morbidity scoring system, and the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0. Secondary endpoints were local control and survival. RESULTS: A total of 40 patients were included, 17 with a centrally located lesion. The lung toxicity-free survival estimate at 2 years was 74% and was related to the location (central vs. peripheral) and the size of the target volume. No dose volumetric parameters could predict the occurrence of lung toxicity. One patient died because of treatment-related toxicity. The 1-year and 2-year local progression-free survival estimates were 97% and 84%, respectively, and were related to stage (T1 vs. T2) related (p = 0.006). Local failure was not more frequent for patients treated in four fractions. The 1-year local progression-free survival estimate dropped below 80% for lesions with a diameter of more than 4 cm. CONCLUSION: The proposed risk-adapted strategy for both centrally and peripherally located lesions showed an acceptable toxicity profile while maintaining excellent local control rates. The correlation between local control and tumor diameter calls for the inclusion of tumor stage as a variable in future study design.

Volumetric imaging by megavoltage computed tomography for assessment of internal organ motion during radiotherapy for cervical cancer.

PURPOSE: To assess the internal organ motion of the cervix and uterus by megavoltage computed tomography (MVCT) during intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Ten patients with Stage IIB-IVA cervical cancer underwent daily MVCT imaging. Internal organ motion was evaluated on 150 pretreatment MVCT images by measuring shifts in their boundaries between the MVCT and kilovoltage (kV) planning CT scan in the anterior, posterior, left and right lateral, and superior and inferior direction. Additional intrafractional patient movement was evaluated on 50 posttreatment MVCT images. RESULTS: Measured cervical motion (mean +/- SD) was 0.4 +/- 10.1 mm in the anterior, -3.0 +/- 6.9 mm in the posterior direction, -3.5 +/- 4.9 mm in the left and 0.2 +/- 4.5 mm in the right lateral direction, 2.2 +/- 8.0 mm in the superior and 0.5 +/- 5.0 mm in the inferior direction. Compared to the cervix, larger uterine motion was observed. Patient movement during treatment was limited to 1.1 +/- 1.3 mm, -0.3 +/- 1.6 mm, and 0.2 +/- 2.3 mm in anteroposterior, laterolateral and superoinferior direction respectively. CONCLUSIONS: MVCT imaging can be used to study patient setup accuracy and cervical and uterine motion during IMRT. This data may be used to refine treatment margins.

Toxicity report of a phase 1/2 dose-escalation study in patients with inoperable, locally advanced nonsmall cell lung cancer with helical tomotherapy and concurrent chemotherapy.

BACKGROUND: The objective of the current study was to evaluate the feasibility and toxicity of radiation dose escalation with concurrent chemotherapy using helical tomotherapy (HT) in patients with inoperable, locally advanced, stage III nonsmall cell lung cancer (LANSCLC) (grading determined according to the American Joint Committee on Cancer 6th edition grading system). METHODS: This phase 1/2 study was designed to determine the maximum tolerated dose (MTD) of radiotherapy in patients with LANSCLC administered concurrently with docetaxel and cisplatin. Radiotherapy was delivered using HT. A dose per fraction escalation was applied starting at 2 grays (Gy), with an increase of 6% per dose cohort (DC). The Radiation Therapy Oncology Group acute radiation morbidity score was used to monitor pulmonary, esophageal, and cardiac toxicity. RESULTS: Dose escalation was performed in 34 patients over 5 DCs to a dose per fraction of 2.48 Gy. No differences were observed in acute toxicity between the different DCs. However, a significant increase in late lung toxicity in DC IV, which received a fraction size of 2.36 Gy, necessitated a halt in further dose escalation with the MTD defined as 2.24 Gy per fraction. The overall incidence of acute grade > or =3 esophageal and pulmonary toxicity was 24% and 3%, respectively (grading determined according to the Radiation Therapy Oncology Group-European Organisation for Research and Treatment of Cancer toxicity scoring system). The overall incidence of late lung toxicity was 21%, but the incidence was an acceptable 13% in DCs I, II, and III. The local response rate was 61% on computed tomography images. CONCLUSIONS: The use of HT to 67.2 Gy with concurrent cisplatin/docetaxel was feasible and resulted in acceptable toxicity. A full phase 2 study has been initiated to establish the true local response rate at the MTD of 2.24 Gy per fraction.