VoiceS: voice quality after transoral CO2 laser surgery versus single vocal cord irradiation for unilateral stage 0 and I glottic larynx cancer-a randomized phase III trial.

BACKGROUND: Surgery and radiotherapy are well-established standards of care for unilateral stage 0 and I early-stage glottic cancer (ESGC). Based on comparative studies and meta-analyses, functional and oncological outcomes after both treatment modalities are similar. Historically, radiotherapy (RT) has been performed by irradiation of the whole larynx. However, only the involved vocal cord is being treated with recently introduced hypofractionated concepts that result in 8 to 10-fold smaller target volumes. Retrospective data argues for an improvement in voice quality with non-inferior local control. Based on these findings, single vocal cord irradiation (SVCI) has been implemented as a routine approach in some institutions for ESGC in recent years. However, prospective data directly comparing SVCI with surgery is lacking. The aim of VoiceS is to fill this gap. METHODS: In this prospective randomized multi-center open-label phase III study with a superiority design, 34 patients with histopathologically confirmed, untreated, unilateral stage 0-I ESGC (unilateral cTis or cT1a) will be randomized to SVCI or transoral CO2-laser microsurgical cordectomy (TLM). Average difference in voice quality, measured by using the voice handicap index (VHI) will be modeled over four time points (6, 12, 18, and 24 months). Primary endpoint of this study will be the patient-reported subjective voice quality between 6 to 24 months after randomization. Secondary endpoints will include perceptual impression of the voice via roughness - breathiness - hoarseness (RBH) assessment at the above-mentioned time points. Additionally, quantitative characteristics of voice, loco-regional tumor control at 2 and 5 years, and treatment toxicity at 2 and 5 years based on CTCAE v.5.0 will be reported. DISCUSSION: To our knowledge, VoiceS is the first randomized phase III trial comparing SVCI with TLM. Results of this study may lead to improved decision-making in the treatment of ESGC. TRIAL REGISTRATION: ClinicalTrials.gov NCT04057209. Registered on 15 August 2019. Cantonal Ethics Committee KEK-BE 2019-01506.

Whole-ventricular irradiation for intracranial germ cell tumors: Dosimetric comparison of pencil beam scanned protons, intensity-modulated radiotherapy and volumetric-modulated arc therapy.

BACKGROUND: Whole-ventricular radiotherapy (WV-RT) followed by a boost to the tumor bed (WV-RT/TB) is recommended for intracranial germ cell tumors (IGCT). As the critical brain areas are mainly in the target volume vicinity, it is unclear if protons indeed substantially spare neurofunctional organs at risk (NOAR). Therefore, a dosimetric comparison study of WV-RT/TB was conducted to assess whether proton or photon radiotherapy achieves better NOAR sparing. METHODS: Eleven children with GCT received 24 Gy(RBE) WV-RT and a boost up to 40 Gy(RBE) in 25 fractions of 1.6 Gy(RBE) with pencil beam scanning proton therapy (PBS-PT). Intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans were generated for these patients. NOAR were delineated and treatment plans were compared for target volume coverage (TVC), homogeneity index (HI), inhomogeneity coefficient (IC) and (N)OAR sparing. RESULTS: TVC was comparable for all three modalities. Compared to IMRT and VMAT, PBS-PT showed statistically significant optimized IC, as well as dose reduction, among others, in mean and integral dose to the: normal brain (-35.2%, -32.7%; -35.2%, -33.0%, respectively), cerebellum (-53.7%, -33.1%; -53.6%, -32.7%) and right temporal lobe (-14.5%, -31.9%; -14.7%, -29.9%). The Willis' circle was better protected with PBS-PT than IMRT (-7.1%; -7.8%). The left hippocampus sparing was higher with IMRT. Compared to VMAT, the dose to the hippocampi, amygdalae and temporal lobes was significantly decreased in the IMRT plans. CONCLUSIONS: Dosimetric comparison of WV-RT/TB in IGCT suggests PBS-PT's advantage over photons in conformality and NOAR sparing, whereas IMRT's superiority over VMAT, thus potentially minimizing long-term sequelae.

Dose calculation of dynamic trajectory radiotherapy using Monte Carlo.

PURPOSE: Using volumetric modulated arc therapy (VMAT) delivery technique gantry position, multi-leaf collimator (MLC) as well as dose rate change dynamically during the application. However, additional components can be dynamically altered throughout the dose delivery such as the collimator or the couch. Thus, the degrees of freedom increase allowing almost arbitrary dynamic trajectories for the beam. While the dose delivery of such dynamic trajectories for linear accelerators is technically possible, there is currently no dose calculation and validation tool available. Thus, the aim of this work is to develop a dose calculation and verification tool for dynamic trajectories using Monte Carlo (MC) methods. METHODS: The dose calculation for dynamic trajectories is implemented in the previously developed Swiss Monte Carlo Plan (SMCP). SMCP interfaces the treatment planning system Eclipse with a MC dose calculation algorithm and is already able to handle dynamic MLC and gantry rotations. Hence, the additional dynamic components, namely the collimator and the couch, are described similarly to the dynamic MLC by defining data pairs of positions of the dynamic component and the corresponding MU-fractions. For validation purposes, measurements are performed with the Delta4 phantom and film measurements using the developer mode on a TrueBeam linear accelerator. These measured dose distributions are then compared with the corresponding calculations using SMCP. First, simple academic cases applying one-dimensional movements are investigated and second, more complex dynamic trajectories with several simultaneously moving components are compared considering academic cases as well as a clinically motivated prostate case. RESULTS: The dose calculation for dynamic trajectories is successfully implemented into SMCP. The comparisons between the measured and calculated dose distributions for the simple as well as for the more complex situations show an agreement which is generally within 3% of the maximum dose or 3mm. The required computation time for the dose calculation remains the same when the additional dynamic moving components are included. CONCLUSION: The results obtained for the dose comparisons for simple and complex situations suggest that the extended SMCP is an accurate dose calculation and efficient verification tool for dynamic trajectory radiotherapy. This work was supported by Varian Medical Systems.

Part 1: Optimization and evaluation of dynamic trajectory radiotherapy.

PURPOSE: Although volumetric modulated arc therapy (VMAT) is a well-accepted treatment technique in radiotherapy using a coplanar delivery approach, VMAT might be further improved by including dynamic table and collimator rotations leading to dynamic trajectory radiotherapy (DTRT). In this work, an optimization procedure for DTRT was developed and the potential benefit of DTRT was investigated for different treatment sites. METHODS: For this purpose, a dedicated optimization framework for DTRT was developed using the Eclipse Scripting Research Application Programming Interface (ESRAPI). The contours of the target and organs at risk (OARs) structures were exported by applying the ESRAPI and were used to determine the fractional volume-overlap of the OARs with the target from several potential beam directions. Thereby, an additional weighting was applied taking into account the relative position of the OAR with respect to the target and radiation beam, that is, penalizing directions where the OAR is proximal to the target. The resulting two-dimensional gantry-table map was used as input for an A* path finding algorithm returning an optimized gantry-table path. Thereby, the process is also taking into account CT scan length and collision restrictions. The A* algorithm was used again to determine the dynamic collimator angle path by optimizing the area between the MLC leaves and the target contour for each gantry-table path leading to gantry-collimator paths. The resulting gantry-table and gantry-collimator paths are combined and serve as input for the intensity modulation optimization using a research VMAT optimizer and the ESRAPI resulting in dynamic trajectories. This procedure was evaluated for five clinically motivated cases: two head and neck, one lung, one esophagus, and one prostate. Final dose calculations were performed using the Swiss Monte Carlo Plan (SMCP). Resulting dose distributions for the DTRT treatment plans and for the standard VMAT plans were compared based on dose distributions and dose volume histogram (DVH) parameters. For this comparison, the dose distribution for the VMAT plans were recalculated using the SMCP. In addition, the suitability of the delivery of a DTRT treatment plan was demonstrated by means of gafchromic film measurements on a TrueBeam linear accelerator. RESULTS: DVHs for the target volumes showed similar or improved coverage and dose homogeneity for DTRT compared with VMAT using equal or less number of dynamic trajectories for DTRT than arcs for VMAT for all cases studied. Depending on the case, improvements in mean and maximum dose for the DTRT plans were achieved for almost all OARs compared with the VMAT plans. Improvements in DTRT treatment plans for mean and maximum dose compared to VMAT plans were up to 16% and 38% relative to the prescribed dose, respectively. The measured and calculated dose values resulted in a passing rate of more than 99.5% for the two-dimensional gamma analysis using 2% and 2 mm criteria and a threshold of 10%. CONCLUSIONS: DTRT plans for different treatment sites were generated and compared with VMAT plans. The delivery is suitable and dose comparisons demonstrate a high potential of DTRT to reduce dose to OARs using less dynamic trajectories than arcs, while target coverage is preserved.

Performance evaluation of a collapsed cone dose calculation algorithm for HDR Ir-192 of APBI treatments.

PURPOSE: Most dose calculations for HDR brachytherapy treatments are based on the AAPM-TG43 formalism. Because patient's anatomy, heterogeneities, and applicator shielding are not considered, the dose calculation based on this formalism is inaccurate in some cases. Alternatively, collapsed cone (CC) methods as well as Monte Carlo (MC) algorithms belong to the model-based dose calculation algorithms, which are expected to improve the accuracy of calculated dose distributions. In this work, the performance of a CC algorithm, ACE in Oncentra Brachy 4.5 (ACE 4.5), has been investigated by comparing the calculated dose distributions to the AAPM-TG43 and MC calculations for 10 HDR brachytherapy accelerated partial breast irradiation treatments (APBI). Comparisons were also performed with a corrected version of ACE 4.5 (ACE 4.5/corr). METHODS: The brachytherapy source microSelectron mHDR-v2 (Elekta Brachytherapy) has been implemented in a MC environment and validated by comparing MC dose distributions simulated in a water phantom of 80 cm in diameter with dose distributions calculated with the AAPM-TG43 algorithm. Dose distributions calculated with ACE 4.5, ACE 4.5/corr, AAPM-TG43 formalism, and MC for 10 APBI patients plans have then been computed and compared using HU scaled densities. In addition, individual dose components have been computed using ACE 4.5, ACE 4.5/corr, and MC, and compared individually. RESULTS: Local differences between MC and AAPM-TG43 calculated dose distributions in a large water phantom are < 1%. When using HUs scaled densities for the breast cancer patients, both accuracy levels of ACE 4.5 overestimate the MC calculated dose distributions for all analyzed dosimetric parameters. In the planning target volume (PTV), ACE 4.5 (ACE 4.5/corr) overestimates on average V100%,PTV by 3% ± 1% (1% ± 1%) and D50,PTV by 3% ± 1% (1% ± 1%) and in the organs at risk D1cc, skin by 4% ± 2% (1% ± 1%), D0.5cc, ribs by 4% ± 2% (0% ± 1%), and D1cc, heart by 8% ± 2% (3% ± 1%) compared to MC. Comparisons of the individual dose components reveals an agreement for the primary component of < 2% local differences for both ACE 4.5 and ACE 4.5/corr. Local differences of about 40% (20%) for the first and residual scatter components where observed when using ACE 4.5 (ACE 4.5/corr). Using uniform densities for one case shows a better agreement between ACE 4.5 and MC for all dosimetric parameters considered in this work. CONCLUSIONS: In general, on the 10 APBI patients the ACE 4.5/corr algorithm results in similar dose distributions as the commonly used AAPM-TG43 within the PTV. However, the accuracy of the ACE 4.5/corr calculated dose distribution is closer to MC than to AAPM-TG43. The differences between commercial version ACE 4.5 and MC dose distributions are mainly located in the first and residual scatter components. In ACE 4.5/corr, the changes done in the algorithm for the scatter components substantially reduce these differences.

Primary tumor volume delineation in head and neck cancer: missing the tip of the iceberg?

BACKGROUND: The aim was to evaluate the geometric and corresponding dosimetric differences between two delineation strategies for head and neck tumors neighboring air cavities. METHODS: Primary gross and clinical tumor volumes (GTV and CTV) of 14 patients with oropharynx or larynx tumors were contoured using a soft tissue window (S). In a second strategy, the same volumes were contoured with an extension to include the parts which became visible on lung window (L). For the calculation of Hausdorff-distances (HD) between contoured volumes of the two strategies, triangular meshes were exported. Two radiotherapy plans with identical goals and optimization parameters were generated for each case. Plan_S were optimized on CTV_S, and Plan_L on CTV_L. The dose coverages of CTV_L and CTV_Δ (CTV_L minus CTV_S) were evaluated in Plan_S. OAR doses were compared among Plan_S and Plan_L. RESULTS: Median three-dimensional HD for GTVs and CTVs were 5.7 (±2.6) and 9.3 (±2.8) mm, respectively. The median volume differences between structures contoured using L and S windows were 9% (±5%) and 9% (±4%) for GTV and CTV, respectively. In 13 out of 14 cases, Plan_S met the plan acceptance criteria for CTV_L. In 8 cases CTV_Δ was covered insufficiently in Plan_S. Mean and median differences in OAR dose-volume histogram parameters between Plan_S and Plan_L were within 3%. CONCLUSION: For the current practice in radiotherapy planning for head and neck cancer, the delineation of L-based volumes seems unnecessary. However, in special settings, where smaller or no PTV margins are used, this approach may play an important role for local control.

Improved VMAT planning for head and neck tumors with an advanced optimization algorithm.

OBJECTIVE: In this study, the "Progressive Resolution Optimizer PRO3" (Varian Medical Systems) is compared to the previous version "PRO2" with respect to its potential to improve dose sparing to the organs at risk (OAR) and dose coverage of the PTV for head and neck cancer patients. MATERIALS AND METHODS: For eight head and neck cancer patients, volumetric modulated arc therapy (VMAT) treatment plans were generated in this study. All cases have 2-3 phases and the total prescribed dose (PD) was 60-72 Gy in the PTV. The study is mainly focused on the phase 1 plans, which all have an identical PD of 54 Gy, and complex PTV structures with an overlap to the parotids. Optimization was performed based on planning objectives for the PTV according to ICRU83, and with minimal dose to spinal cord, and parotids outside PTV. In order to assess the quality of the optimization algorithms, an identical set of constraints was used for both, PRO2 and PRO3. The resulting treatment plans were investigated with respect to dose distribution based on the analysis of the dose volume histograms. RESULTS: For the phase 1 plans (PD = 54 Gy) the near maximum dose D2% of the spinal cord, could be minimized to 22 ± 5 Gy with PRO3, as compared to 32 ± 12 Gy with PRO2, averaged for all patients. The mean dose to the parotids was also lower in PRO3 plans compared to PRO2, but the differences were less pronounced. A PTV coverage of V95% = 97 ± 1% could be reached with PRO3, as compared to 86 ± 5% with PRO2. In clinical routine, these PRO2 plans would require modifications to obtain better PTV coverage at the cost of higher OAR doses. CONCLUSION: A comparison between PRO3 and PRO2 optimization algorithms was performed for eight head and neck cancer patients. In general, the quality of VMAT plans for head and neck patients are improved with PRO3 as compared to PRO2. The dose to OARs can be reduced significantly, especially for the spinal cord. These reductions are achieved with better PTV coverage as compared to PRO2. The improved spinal cord sparing offers new opportunities for all types of paraspinal tumors and for re-irradiation of recurrent tumors or second malignancies.

High dose-rate versus low dose-rate brachytherapy for lip cancer.

PURPOSE: To analyze the outcome after low-dose-rate (LDR) or high-dose-rate (HDR) brachytherapy for lip cancer. METHODS AND MATERIALS: One hundred and three patients with newly diagnosed squamous cell carcinoma of the lip were treated between March 1985 and June 2009 either by HDR (n = 33) or LDR brachytherapy (n = 70). Sixty-eight patients received brachytherapy alone, and 35 received tumor excision followed by brachytherapy because of positive resection margins. Acute and late toxicity was assessed according to the Common Terminology Criteria for Adverse Events 3.0. RESULTS: Median follow-up was 3.1 years (range, 0.3-23 years). Clinical and pathological variables did not differ significantly between groups. At 5 years, local recurrence-free survival, regional recurrence-free survival, and overall survival rates were 93%, 90%, and 77%. There was no significant difference for these endpoints when HDR was compared with LDR brachytherapy. Forty-two of 103 patients (41%) experienced acute Grade 2 and 57 of 103 patients (55%) experienced acute Grade 3 toxicity. Late Grade 1 toxicity was experienced by 34 of 103 patients (33%), and 5 of 103 patients (5%) experienced late Grade 2 toxicity; no Grade 3 late toxicity was observed. Acute and late toxicity rates were not significantly different between HDR and LDR brachytherapy. CONCLUSIONS: As treatment for lip cancer, HDR and LDR brachytherapy have comparable locoregional control and acute and late toxicity rates. HDR brachytherapy for lip cancer seems to be an effective treatment with acceptable toxicity.

VMC++ validation for photon beams in the energy range of 20-1000 keV.

PURPOSE: In high energy teletherapy, VMC++ is known to be a very accurate and efficient Monte Carlo (MC) code. In principle, the MC method is also a powerful dose calculation tool in other areas in radiation oncology, e.g., brachytherapy or orthovoltage radiotherapy. However, VMC++ is not validated for the low-energy range of such applications. This work aims in the validation of the VMC++ MC code for photon beams in the energy range between 20 and 1000 keV. METHODS: Dose calculations were performed in different 40 x 40 x 40 cm3 phantoms of different materials. Dose distributions of monoenergetic (ranging from 20 to 1000 keV) 10 x 10 and 2 x 2 cm2 parallel beams were calculated. Voxel sizes of 4 x 4 x 4 and 1 x 1 x 1 mm3 were used for the dose calculations. The resulting dose distributions were compared to those calculated using EGSnrc, which is used as a golden standard in this work. RESULTS: At energies between 100 and 1000 keV, EGSnrc and VMC++ calculated dose distributions agree within the statistical uncertainty of about 1% (1sigma). At energies < or = 50 keV, dose differences of up to 1.6% (in % of D(max)) occur when VMC++ and EGSnrc are compared. Turning off Rayleigh scattering, binding effects for Compton scattering, and the atomic relaxation after photoelectric absorption in EGSnrc (all not implemented in VMC++) leads to an agreement between both MC codes within statistical uncertainty. Further, using the KERMA approximation feature implemented in VMC++ leads to very efficient simulations in the energy range between 20 and 1000 keV. CONCLUSIONS: Further improvements for very low energies in accuracy of VMC++ could be achieved by implementing Rayleigh scattering, binding effects for Compton scattering, and the atomic relaxation after photoelectric absorption. Implementation into VMC++ of KERMA approximation has been validated.