Comparison of MR-guided radiotherapy accumulated doses for central lung tumors with non-adaptive and online adaptive proton therapy.

BACKGROUND: Stereotactic body radiation therapy (SBRT) of central lung tumors with photon or proton therapy has a risk of increased toxicity. Treatment planning studies comparing accumulated doses for state-of-the-art treatment techniques, such as MR-guided radiotherapy (MRgRT) and intensity modulated proton therapy (IMPT), are currently lacking. PURPOSE: We conducted a comparison of accumulated doses for MRgRT, robustly optimized non-adaptive IMPT, and online adaptive IMPT for central lung tumors. A special focus was set on analyzing the accumulated doses to the bronchial tree, a parameter linked to high-grade toxicities. METHODS: Data of 18 early-stage central lung tumor patients, treated at a 0.35 T MR-linac in eight or five fractions, were analyzed. Three gated treatment scenarios were compared: (S1) online adaptive MRgRT, (S2) non-adaptive IMPT, and (S3) online adaptive IMPT. The treatment plans were recalculated or reoptimized on the daily imaging data acquired during MRgRT, and accumulated over all treatment fractions. Accumulated dose-volume histogram (DVH) parameters of the gross tumor volume (GTV), lung, heart, and organs-at-risk (OARs) within 2 cm of the planning target volume (PTV) were extracted for each scenario and compared in Wilcoxon signed-rank tests between S1 & S2, and S1 & S3. RESULTS: The accumulated GTV D98% was above the prescribed dose for all patients and scenarios. Significant reductions (p < 0.05) of the mean ipsilateral lung dose (S2: -8%; S3: -23%) and mean heart dose (S2: -79%; S3: -83%) were observed for both proton scenarios compared to S1. The bronchial tree D0.1cc was significantly lower for S3 (S1: 48.1 Gy; S3: 39.2 Gy; p = 0.005), but not significantly different for S2 (S2: 45.0 Gy; p = 0.094), compared to S1. The D0.1cc for S2 and S3 compared to S1 was significantly (p < 0.05) smaller for OARs within 1-2 cm of the PTV (S1: 30.2 Gy; S2: 24.6 Gy; S3: 23.1 Gy), but not significantly different for OARs within 1 cm of the PTV. CONCLUSIONS: A significant dose sparing potential of non-adaptive and online adaptive proton therapy compared to MRgRT for OARs in close, but not direct proximity of central lung tumors was identified. The near-maximum dose to the bronchial tree was not significantly different for MRgRT and non-adaptive IMPT. Online adaptive IMPT achieved significantly lower doses to the bronchial tree compared to MRgRT.

A comprehensive Monte Carlo study of out-of-field secondary neutron spectra in a scanned-beam proton therapy gantry room.

PURPOSE: To simulate secondary neutron radiation fields that had been measured at different relative positions during phantom irradiation inside a scanning proton therapy gantry treatment room. Further, to identify origin, energy distribution, and angular emission of the secondary neutrons as a function of proton beam energy. METHODS: The FLUKA Monte Carlo code was used to model the relevant parts of the treatment room in a scanned pencil beam proton therapy gantry including shielding walls, floor, major metallic gantry-components, patient table, and a homogeneous PMMA target. The proton beams were modeled based on experimental beam ranges in water and spot shapes in air. Neutron energy spectra were simulated at 0°, 45°, 90° and 135° relative to the beam axis at 2m distance from isocenter for monoenergetic 11×11cm2 fields from 200MeV, 140MeV, 75MeV initial proton beams, as well as for 118MeV protons with a 5cm thick PMMA range shifter. The total neutron spectra were scored for these four positions and proton energies. FLUKA neutron spectra simulations were crosschecked with Geant4 simulations using initial proton beam properties from FLUKA-generated phase spaces. Additionally, the room-components generating secondary neutrons in the room and their contributions to the total spectrum were identified and quantified. RESULTS: FLUKA and Geant4 simulated neutron spectra showed good general agreement with published measurements in the whole simulated neutron energy range of 10-10 to 103MeV. As in previous studies, high-energy (E≥19.6MeV) neutrons from the phantom are most prevalent along 0°, while thermalized (1meV≤E<0.4eV) and fast (100keV≤E<19.4MeV) neutrons dominate the spectra in the lateral and backscatter direction. The iron of the large bending magnet and its counterweight mounted on the gantry were identified as the most determinant sources of secondary fast-neutrons, which have been lacking in simplified room simulations. CONCLUSIONS: The results helped disentangle the origin of secondary neutrons and their dominant contributions and were strengthened by the fact that a cross comparison was made using two independent Monte Carlo codes. The complexity of such room model can in future be limited using the result. They may further be generalized in that they can be used for an assessment of neutron fields, possibly even at facilities where detailed neutron measurements and simulations cannot be performed. They may also help to design future proton therapy facilities and to reduce unwanted radiation doses from secondary neutrons to patients.

Gel dosimetry for three dimensional proton range measurements in anthropomorphic geometries.

Proton beams used for radiotherapy have potential for superior sparing of normal tissue, although range uncertainties are among the main limiting factors in the accuracy of dose delivery. The aim of this study was to benchmark an N-vinylpyrrolidone based polymer gel to perform three-dimensional measurement of geometric proton beam characteristics and especially to test its suitability as a range probe in combination with an anthropomorphic phantom. For single proton pencil beams as well as for 3×3cm2 mono-energy layers depth dose profiles, lateral dose distribution at different depths and proton range were evaluated in simple cubic gel phantoms at different energies from 75 to 115MeV and different dose levels. In addition, a 90MeV mono-energetic beam was delivered to an anthropomorphic 3D printed head phantom, which was filled with gel. Subsequently, all phantoms underwent magnetic resonance imaging using an axial pixel size of 0.68-0.98mm and with slice thicknesses of 2 or 3mm to derive a 3-dimensional distribution of the T2 relaxation time, which correlates with radiation dose. Indices describing lateral dose distribution and proton range were compared against predictions from a treatment planning system (TPS, for cubic and head phantoms) and Monte Carlo simulations (MC, for the head phantom) after manual rigid co-registration with the T2 relaxation time datasets. For all pencil beams, the FWHM agreement with TPS was better than 1mm or 7%. For the mono-energetic layer, the agreement with TPS in this respect was even better than 0.3mm in each case. With respect to range, results from gel measurements differed no more than 0.9mm (1.6%) from values predicted by TPS. In case of the anthropomorphic phantom, deviations with respect to a nominal range of about 61mm as well as in FWHM were slightly higher, namely within 1.0mm and 1.1mm respectively. Average deviations between gel and TPS/MC were similar (-0.3mm±0.4mm/-0.2±0.5mm). In conclusion, polymer gel dosimetry was found to be a valuable tool to determine geometric proton beam properties three-dimensionally and with high spatial resolution in simple cubic as well as in a more complex anthropomorphic phantom. Post registration range errors of the order of 1mm could be achieved. The additional registration uncertainty (95%) was 1mm.

Systematic out-of-field secondary neutron spectrometry and dosimetry in pencil beam scanning proton therapy.

BACKGROUND AND PURPOSE: Systematic investigation of the energy and angular dependence of secondary neutron fluence energy distributions and ambient dose equivalents values (H*(10)) inside a pencil beam scanning proton therapy treatment room using a gantry. MATERIALS AND METHODS: Neutron fluence energy distributions were measured with an extended-range Bonner sphere spectrometer featuring ³He proportional counters, at four positions at 0°, 45°, 90°, and 135° with respect to beam direction and at a distance of 2 m from the isocenter. The energy distribution of secondary neutrons was investigated for initial proton beam energies of 75 MeV, 140 MeV, and 200 MeV, respectively, using a 2D scanned irradiation field of 11 × 11 cm² delivered to a 30 × 30 × 30 cm³ PMMA phantom. Additional measurements were performed at a proton energy of 118 MeV including a 5 cm range-shifter (PMMA), yielding a Bragg peak position similar to that of 75 MeV protons. RESULTS: Ambient dose equivalent values from 0.3 µSv/Gy (75 MeV; 90°) to 24 µSv/Gy (200 MeV; 0°) were measured inside the treatment room at a distance of 2 m from the isocenter. H*(10) values were lower (by factors of up to 7.2 (at 45°)) at 75 MeV compared to those at 118 MeV with the 5 cm range-shifter. At 0° and 45°, an evaporation peak was found in the measured neutron fluence energy distributions, at neutron energies around MeV, which contributes about 50% to total H*(10) values, for all investigated proton beam energies. CONCLUSIONS: This study showed a pronounced increase of secondary neutron H*(10) values inside the proton treatment room with increasing proton energy without beam modifiers. For example, in beam direction this increase was about a factor of 50 when protons of 75 MeV and 200 MeV were compared. The existence of a peak of secondary neutrons in the MeV region was demonstrated in beam direction (0°). This peak is due to evaporation neutrons produced in the existing surrounding materials such as those used for the gantry. Therefore, any simulation of the secondary neutrons within a proton treatment room must take these materials into account. In addition, the results obtained here show that the use of a range-shifter increases the production of secondary neutrons inside the treatment room. Using a range-shifter, the higher neutron doses observed mainly result from the higher incident proton energy (118 MeV instead of 75 MeV when no range-shifter was used), due to higher neutron production cross-sections.

Dosimetry intercomparison of four proton therapy institutions in Germany employing spot scanning.

AIM: To verify the consistency of dose and range measurement in an interinstitution comparison among proton therapy institutions in Germany which use the pencil-beam scanning technique. METHODS: Following a peer-to-peer approach absorbed dose and range have been intercompared in several missions at two hosting centers with two or three visiting physics teams of participating institutions using their own dosimetry equipment. A meta-analysis has been performed integrating the results of the individual missions. Dose has been determined with ionization chambers according to the dosimetry protocol IAEA TRS-398. For determination of the depth of the distal 80% dose the teams used either a scanning water phantom, a variable water column or a multi-layer ionization chamber. RESULTS: The systematic deviation between measured doses of the participating institutions is less than 1%. Ranges differ systematically less than 0.4mm. CONCLUSIONS: The match of measured dose and range is better than expected from the respective uncertainties. As all physics teams agree on the assessment of absorbed dose and range, an important prerequisite for a start of joint clinical studies is fulfilled.

Assessing a set of optimal user interface parameters for intensity-modulated proton therapy planning.

The purpose was to identify an optimal set of treatment planning parameters and a minimal necessary dose matrix resolution for treatment planning with spot-scanned protons. Treatment plans based on different combinations of planning parameters and dose grid resolutions (DG) were calculated in a homogeneous geometric phantom for three cubic targets of different size: 8, 64 and 244 cm3. The proton dose was delivered by one single beam. Treatment plans were compared in terms of dose profiles parallel to and perpendicular to the central beam axis, as well as by dose homogeneity and conformity measures. Irrespective of target size, the dose homogeneity and conformity were comparable if the distance between spot layers was in the order of the width of a single Bragg peak, and the lateral distance between spots did not exceed two times the spot sigma. If the distance between spot layers was considerably larger than the width of the Bragg peak, the homogeneity index increased. For the small target, this index escalated from values around 5% to 12% in extreme, and to more than 20% for the two larger targets. Furthermore, the width of the 95% isodose increased. Similar results were found for the variation of the parameter determining the lateral spacing between proton dose spots. The average difference of dose profiles with respect to the profile for a DG of 1mm was below 3% for all considered settings up to a DG of 6 mm. However, a DG of less than 2-3 mm is required to keep the maximum deviation below this limit. The tests performed in this study are necessary to prevent systematic errors from spot-scanning proton therapy planning. A separation of dose spots in the dimensions of the Bragg peak in the longitudinal direction and no more than two times the spot sigma in the lateral direction were found to be adequate for IMPT treatment planning in a homogeneous phantom. A DG of 2-3 mm is necessary to accurately resolve the steep dose gradients of proton beams.

Assessment of improved organ at risk sparing for advanced cervix carcinoma utilizing precision radiotherapy techniques.

PURPOSE: To evaluate the potential benefit of proton therapy and photon based intensity-modulated radiotherapy in comparison to 3-D conformal photon radiotherapy (3D-CRT) in locally advanced cervix cancer. PATIENTS AND METHODS: In five patients with advanced cervix cancer 3D-CRT (four-field box) was compared with intensity modulated photon (IMXT) and proton therapy (IMPT) as well as proton beam therapy (PT) based on passive scattering. Planning target volumes (PTVs) included primary tumor and pelvic and para-aortic lymph nodes. Dose-volume histograms (DVHs) were analyzed for the PTV and various organs at risk (OARs) (rectal wall, bladder, small bowel, colon, femoral heads, and kidneys). In addition dose conformity, dose inhomogeneity and overall volumes of 50% isodoses were assessed. RESULTS: All plans were comparable concerning PTV parameters. Large differences between photon and proton techniques were seen in volumes of the 50% isodoses and conformity indices. DVH for colon and small bowel were significantly improved with PT and IMPT compared to IMXT, with D(mean) reductions of 50-80%. Doses to kidneys and femoral heads could also be substantially reduced with PT and IMPT. Sparing of rectum and bladder was superior with protons as well but less pronounced. CONCLUSION: Proton beam RT has significant potential to improve treatment related side effects in the bowel compared to photon beam RT in patients with advanced cervix carcinoma.

Abdominal cancer during early childhood: a dosimetric comparison of proton beams to standard and advanced photon radiotherapy.

PURPOSE: Evaluation of dosimetric benefits of advanced radiotherapy techniques for the treatment of abdominal lesions during early childhood. PATIENTS AND METHODS: Treatment planning was performed for five Neuroblastoma (NBL) and four Wilms Tumor (WT) patients. Opposing fields (2F), photon intensity modulated radiotherapy (IMXT) and two proton techniques (passively scattered (PT) and scanned beams (IMPT)) were considered. Averaged dose-volume histograms, associated dosimetric parameters and a radiobiological model for the estimation of the therapy related carcinogenic effect were evaluated. RESULTS: With respect to the 2F technique, both proton techniques enabled to reduce mean liver and kidney dose by 40-60%; Organ fractions irradiated at the level of the tolerance dose were reduced by 65% for kidneys and 75% for the liver in NBL patients and by additional 10% for WT patients. IMXT enabled to reduce parameters related to the steep high-dose gradient, e.g., V(15Gy) for the kidneys was reduced by a factor 2-3 compared to 2F. V(12Gy) was reduced by 40% in the liver. On the other side, the improvement of those parameters characterizing the low isodose domain was limited for IMXT. The risk for radiation-induced secondary cancer was doubled for IMXT and even more increased for PT if secondary neutrons were taken into account, while this risk remained the same or was reduced by IMPT with respect to 2F. CONCLUSIONS: Proton beams improved all dosimetric parameters for NBL and WT patients compared to photon techniques. This improvement was limited for IMXT mainly to parameters related to the steep high-dose gradient. Further research is needed to minimize uncertainties for secondary cancer estimations.

Image-guided radiotherapy for cervix cancer: high-tech external beam therapy versus high-tech brachytherapy.

PURPOSE: Many studies comparing external-beam therapy (EBT) and brachytherapy (BT) are biased because advanced EBT is compared with conventional BT. This study compares high-tech EBT against high-tech BT. METHODS AND MATERIALS: Nine patients were selected with locally advanced cervix cancer, representing typical clinical situations according to initial tumor extension and response after EBT. Patients were treated either with intracavitary, combined interstitial/intracavitary, or complex interstitial BT. Gross tumor volume, high-risk clinical target volume (CTV), intermediate-risk CTV, bladder, rectum, and sigmoid were delineated. Magnetic resonance-guided BT planning was manually optimized with respect to organ dose limits. Margins (3 and 5 mm) were added to BT CTVs to construct planning target volumes (PTVs) for EBT. Inversely planned EBT with photons (IMRT) and protons (IMPT) was challenged to deliver the highest possible doses to PTVs while respecting D(1cc) and D(2cc) limits from BT, assuming the same fractionation (4 x 7 Gy). The D90 for target structures and normal tissue volumes receiving fractionated doses between 3 and 7 Gy were compared. RESULTS: High-risk CTV doses depended on the clinical situation and radiation quality. If IMRT was limited to D(2cc) and D(1cc) from BT, the D90 for high-risk PTV and intermediate-risk PTV was mostly lower. Volumes receiving 60 Gy (in equivalent dose in 20 Gy fractions) were approximately twice as large for IMRT compared with BT. For IMPT, this volume ratio was lower. Planning target volume doses of IMPT plans with 3-mm margins were comparable to those with BT. Gross tumor volume doses were mostly lower for both IMRT and IMPT. CONCLUSION: For benchmarking high-tech EBT, high-tech BT techniques have to be used. For cervix cancer boost treatments, both IMRT and IMPT seem to be inferior to advanced BT.

Can protons improve SBRT for lung lesions? Dosimetric considerations.

BACKGROUND AND PURPOSE: The aim of the present study was to investigate potential dosimetric benefits of proton therapy for hypofractionated stereotactic body radiotherapy (SBRT). MATERIALS AND METHOD: Twelve patients undergoing hypofractionated SBRT at the Medical University Vienna were selected. Passively scattered protons (PT) and intensity modulated proton therapy (IMPT) were evaluated against a conformal photon technique (3D-CRT), assuming a fractionation of 3x15Gy, prescribed to the 65% isodose. For all treatment techniques shallow breathing with abdominal compression (SB+AC) was compared with a deep inspiration breath hold technique (DIBH). Treatment planning was done with XiO (CMS, USA). Target conformity, dose-volume histograms (DVH) and various associated dosimetric parameters were considered for the planning target volume (PTV), lung, heart and esophagus. RESULTS: For both breathing conditions conformity indices were very similar. They were between 0.75 and 0.78 for IMPT and 3D-CRT and around 0.55 for PT using 2-3 beams. Irrespective of treatment modality, DVHs for the ipsilateral lung were improved with the DIBH technique. For the PT technique, the 2Gy isodose (V2Gy) covered on average 7-9% less lung volume compared to 3D-CRT, for IMPT this reduction was more than 10%. Volumes covered the 4 and 6Gy isodoses were 2-4% smaller for IMPT, but very similar for PT and 3D-CRT. Both proton techniques achieved full sparing of the contralateral lung and superior sparing of the heart. Maximum doses to the heart and esophagus were on average around 3Gy for 3D-CRT and almost 0Gy for both proton techniques. For 3D-CRT average V2Gy values for the heart could be reduced from 64% in shallow breathing to 34% in DIBH. V2Gy for protons was negligible. CONCLUSIONS: Only small dosimetric differences were found between photons and protons for SBRT of lung lesions. Whether these small dosimetric benefits translate in reduced side effects or have the potential to improve local control rates remains to be demonstrated in clinical studies.

Factors influencing bowel sparing in intensity modulated whole pelvic radiotherapy for gynaecological malignancies.

BACKGROUND AND PURPOSE: To evaluate the influence of uterus and bladder size on large and small bowel sparing with intensity modulated whole pelvic radiotherapy (IM-WPRT) in gynecologic patients. PATIENTS AND METHODS: Twenty patients were selected; 10 women with cervical cancer treated with definitive radiotherapy (group 'DEF') and 10 endometrial cancer patients treated postoperatively (group 'POST'). Bladder, rectal wall, small (SB) and large bowel (LB) were delineated as organs at risk. A conformal four field technique and a seven field IMRT plan (prescription dose 50.4 Gy) were compared in terms of DVH and various target parameters. RESULTS: At doses between 40 and 50.4 Gy statistically significant improvements (P<0.05) were observed for IM-WPRT for irradiated volume of rectal wall and bladder. In both patient groups, with IMRT the average irradiated volume of SB was reduced by a factor of 6 at 50.4Gy. This ratio was 2 for LB. In the DEF group the effect of SB-sparing with IMRT correlated with bladder size (correlation coefficient 0.70) while it did not correlate in the postoperative group. The effect of LB-sparing decreased with increasing bladder size in both groups but the impact of IMRT was larger for postoperative patients. CONCLUSIONS: IMRT significantly reduced the absolute volume of rectal wall, bladder and bowel irradiated at the prescribed dose level in gynaecologic patients. Main differences between POST and DEF patients receiving IM-WPRT were absolute volumes of LB irradiated to doses between 35 and 50Gy, suggesting an impact of intact uterus on LB volume in the pelvis. POST patients seem to benefit most from elective nodal IMRT. Bladder filling is an important co-factor influencing the benefit of IMRT with respect to OAR sparing.