Intensity Modulated Arc Therapy Research Articles

Comparative analysis of simultaneous integrated boost and sequential boost radiotherapy in node-positive cervical cancer: dosimetric and radiobiological considerations.

For locally advanced cervical cancer, the standard therapeutic approach involves concomitant chemoradiation therapy, supplemented by a brachytherapy boost. Moreover, an external beam radiotherapy (RT) boost should be considered for treating gross lymph node (LN) volumes. Two boost approaches exist with Volumetric Intensity Modulated Arc Therapy (VMAT): Sequential (SEQ) and Simultaneous Integrated Boost (SIB). This study undertakes a comprehensive dosimetric and radiobiological comparison between these two boost strategies. The study encompassed ten patients who underwent RT for cervical cancer with node-positive disease. Two sets of treatment plans were generated for each patient: SIB-VMAT and SEQ-VMAT. Dosimetric as well as radiobiological parameters including tumour control probability (TCP) and normal tissue complication probability (NTCP) were compared. Both techniques were analyzed for two different levels of LN involvement - only pelvic LNs and pelvic with para-aortic LNs. Statistical analysis was performed using SPSS software version 25.0. SIB-VMAT exhibited superior target coverage, yielding improved doses to the planning target volume (PTV) and gross tumour volume (GTV). Notably, SIB-VMAT plans displayed markedly superior dose conformity. While SEQ-VMAT displayed favorable organ sparing for femoral heads, SIB-VMAT appeared as the more efficient approach for mitigating bladder and bowel doses. TCP was significantly higher with SIB-VMAT, suggesting a higher likelihood of successful tumour control. Conversely, no statistically significant difference in NTCP was observed between the two techniques. This study's findings underscore the advantages of SIB-VMAT over SEQ-VMAT in terms of improved target coverage, dose conformity, and tumour control probability. In particular, SIB-VMAT demonstrated potential benefits for cases involving para-aortic nodes. It is concluded that SIB-VMAT should be the preferred approach in all cases of locally advanced cervical cancer.

Could a low-dose definitive radiation therapy be the optimal treatment for choroidal hemangioma?

PurposeTo determine the efficacy of low-dose intensity-modulated radiation therapy (IMRT)/volumetric intensity-modulated arc therapy (VMAT) in the treatment of symptomatic choroidal hemangioma (CH). Materials and methodsFifty-three consecutive patients with CH were retrospectively reviewed. All the patients underwent IMRT/VMAT as a unique treatment. Resolution of subretinal fluid (SRF), improvement of best-corrected visual acuity (BCVA), and reduction in tumor thickness were compared before and after radiotherapy. ResultsAfter definitive radiotherapy, 100 % of SRF and 76.7 % of exudative retinal detachment were resolved. 56.6 % of BCVA improvement in more than two lines was observed. The mean best-corrected visual acuity was 20/280 (range, 20/1200–20/40) at diagnosis and 20/100 (range, 20/1200–20/20) after treatment. The mean tumor thickness decreased significantly from 3.8 mm initially to 1.2 mm after treatment (p < 0.01). 66.0 % of patients were delivered with 21.6 Gy (range, 21.6–42 Gy), 84.9 % of fractional dose was 1.8 Gy (range, 1.8–2 Gy). No radiation-induced keratitis, retinopathy, or optic neuropathy were observed. Initial vision (p = 0.042), duration time of vision (p = 0.004), and tumor thickness (p = 0.049) were prognostic factors for vision recovery. ConclusionLow-dose IMRT/VMAT could effectively induce involution of the CH, with reduction of subretinal fluid and relief of damage to the neurosensory retina, which is an effective treatment mode for CH.

A Dosimetric Comparative Study of Carbon-Ion Radiotherapy Versus X-ray Volumetric Modulated Arc Therapy for Stage III Non-Small-Cell Lung Cancer.

Compared to photon beam, carbon-ion radiotherapy (CIRT) has both physical and biological advantages. To examine whether two-dimensional (2D) CIRT is dosimetrically superior to photon beam volume-modulated arc therapy (VMAT) in protecting the normal tissues for stage III non-small-cell lung cancer (NSCLC). A retrospective study was conducted. Thirteen patients with stage III NSCLC treated in our center with curative CIRT and a sham photon beam VMAT treatment planning with the same normal tissue dose constraints were included for analysis. Target dose distributions and the homogeneity index (HI) within the planning target volumes were compared. Both CIRT and VMAT plans have good tumor coverage with no significant differences in D98, D95, and D50 of Planning target volume 1 (PTV1) between the two plans. The HIs between the two plans are similar. The HI of PTV2 is superior in the CIRT plan (CIRT vs. VMAT: 0.08 vs. 0.16, P < 0.05). In general, CIRT results in a lower dose of the organ-at-risk (OAR) than the photon plans. The V5, V10, V20, V30, V40, and Dmean of the contralateral lung in the CIRT plan are significantly lower than that of the photon VMAT. For the ipsilateral lung, the V5 of CIRT is significantly lower. The CIRT also had significantly lower spinal cord Dmax, esophageal Dmean and V50, V10 and V30 of bone, and V50 of the trachea and bronchial tree. Compared with photon VMAT, 2D-CIRT using the passive beam scanning technique significantly reduces the radiation dose to the OARs in curative radiotherapy of stage III NSCLC, suggesting a better protection of the normal tissues.

Multi-institutional investigation into the robustness of intra-cranial multi-target stereotactic radiosurgery plans to delivery errors.

The use of modulated techniques for intra-cranial stereotactic radiosurgery (SRS) results in highly modulated fields with small apertures, which may be susceptible to uncertainties in the delivery device. This study aimed to quantify the impact of simulated delivery errors on treatment plan dosimetry and how this is affected by treatment planning system (TPS), plan geometry, delivery technique, and plan complexity. A beam modelling error was also included as context to the dose uncertainties due to treatment delivery errors. Delivery errors were assessed for multiple-target brain SRS plans obtained through the Trans-Tasman Radiation Oncology Group (TROG) international treatment planning challenge (2018). The challenge dataset consisted of five intra-cranial targets, each with a prescription of 20Gy. Of the final dataset of 54 plans, 51 were created using the volumetric modulated arc therapy (VMAT) technique and three used intensity modulated arc therapy (IMRT). Thirty-five plans were from the Varian Eclipse TPS, 17 from Elekta Monaco TPS, and one plan each from RayStation and Philips Pinnacle TPS. The errors introduced included: monitor unit calibration errors, multi-leaf collimator (MLC) bank offset, single MLC leaf offset, couch rotations, and collimator rotations. Dosimetric leaf gap (DLG) error was also included as a beam modelling error. Dose to targets was assessed via dose covering 98% of planning target volume (PTV) (D98%), dose covering 2% of PTV (D2%), and dose covering 99% of gross tumor volume (GTV) (D99%). Dose to organs at risk (OARs) was assessed using the volume of normal brain receiving 12Gy (V12Gy), mean dose to normal brain, and maximum dose covering 0.03cc brainstem (D0.03cc). Plan complexity was also assessed via edge metric, modulation complexity score (MCS), mean MLC gap, mean MLC speed, and plan modulation (PM). PTV D98% showed high robustness on average to most errors with the exception of a bank shift of 1.0mm and large rotational errors ≥1.0° for either the couch or collimator. However, in some cases, errors close to or within generally accepted machine tolerances resulted in clinically relevant impacts. The greatest impact upon normal brain V12Gy, mean dose to normal brain, and D0.03cc brainstem was found for DLG error in alignment with other recent studies. All delivery errors had on average a minimal impact across these parameters. Comparing plans from the Monaco TPS and the Eclipse TPS, showed a lesser increase to V12Gy, mean dose to normal brain, and D0.03cc brainstem for Monaco plans (p<0.01) when DLG error was simulated. Monaco plans also correlated to lower plan complexity. Using Spearman's correlation coefficient (r) a strong negative correlation (r≤-0.8) was found between the mean MLC gap and dose to OARs for DLG errors. Reducing MLC complexity and using larger mean MLC gaps is recommended to improve plan robustness and reduce sensitivity to delivery and modelling errors. For cases in which the calculated dose distribution or dose indices are close to the clinically acceptable limits, this is especially important.

Stereotactic body radiotherapy with volumetric intensity-modulated arc therapy and flattening filter-free beams: dosimetric considerations.

The present study comparatively evaluates the impact of energy-matched flattening filter-free (FFF) photon beams with different energy levels on the physical-dosimetric quality of lung and liver stereotactic body radiotherapy (SBRT) treatment plans. For this purpose, 54different lung and liver lesions from 44patients who had already received SBRT combined with volumetric modulated arc therapy (VMAT) were included in this retrospective planning study. Planning computed tomography scans already available were used for the renewed planning with 6MV, 6MV-FFF, 10MV, and 10MV-FFF under constant planning objectives. The treatment delivery data, dosimetric distributions, and dose-volume histograms as well as parameters such as the conformity index and gradient indices were the basis for the evaluation and comparison of treatment plans. Asignificant reduction of beam-on time (BOT) was achieved due to the high dose rates of FFF beams. In addition, we showed that for FFF beams compared to flattened beams of the same energy level, smaller planning target volumes (PTV) require fewer monitor units (MU) than larger PTVs. An equal to slightly superior target volume coverage and sparing of healthy tissue as well as organs at risk in both lung and liver lesions were found. Significant differences were seen mainly in the medium to lower dose range. We found that FFF beams together with VMAT represent an excellent combination for SBRT of lung or liver lesions with shortest BOT for 10MV-FFF but significant dose savings for 6MV-FFF in lung lesions.

Radiation Planning Assistant - A Web-based Tool to Support High-quality Radiotherapy in Clinics with Limited Resources.

Access to radiotherapy worldwide is limited. The Radiation Planning Assistant (RPA) is a fully automated, web-based tool that is being developed to offer fully automated radiotherapy treatment planning tools to clinics with limited resources. The goal is to help clinical teams scale their efforts, thus reaching more patients with cancer. The user connects to the RPA via a webpage, completes a Service Request (prescription and information about the radiotherapy targets), and uploads the patient's CT image set. The RPA offers two approaches to automated planning. In one-step planning, the system uses the Service Request and CT scan to automatically generate the necessary contours and treatment plan. In two-step planning, the user reviews and edits the automatically generated contours before the RPA continues to generate a volume-modulated arc therapy plan. The final plan is downloaded from the RPA website and imported into the user's local treatment planning system, where the dose is recalculated for the locally commissioned linac; if necessary, the plan is edited prior to approval for clinical use.

MRI-based inter- and intrafraction motion analysis of the pancreatic tail and spleen as preparation for adaptive MRI-guided radiotherapy in neuroblastoma

BackgroundIn pediatric radiotherapy treatment planning of abdominal tumors, dose constraints to the pancreatic tail/spleen are applied to reduce late toxicity. In this study, an analysis of inter- and intrafraction motion of the pancreatic tail/spleen is performed to estimate the potential benefits of online MRI-guided radiotherapy (MRgRT).Materials and methodsTen randomly selected neuroblastoma patients (median age: 3.4 years), irradiated with intensity-modulated arc therapy at our department (prescription dose: 21.6/1.8 Gy), were retrospectively evaluated for inter- and intrafraction motion of the pancreatic tail/spleen. Three follow-up MRIs (T2- and T1-weighted ± gadolinium) were rigidly registered to a planning CT (pCT), on the vertebrae around the target volume. The pancreatic tail/spleen were delineated on all MRIs and pCT. Interfraction motion was defined as a center of gravity change between pCT and T2-weighted images in left-right (LR), anterior-posterior (AP) and cranial-caudal (CC) direction. For intrafraction motion analysis, organ position on T1-weighted ± gadolinium was compared to T2-weighted. The clinical radiation plan was used to estimate the dose received by the pancreatic tail/spleen for each position.ResultsThe median (IQR) interfraction motion was minimal in LR/AP, and largest in CC direction; pancreatic tail 2.5 mm (8.9), and spleen 0.9 mm (3.9). Intrafraction motion was smaller, but showed a similar motion pattern (pancreatic tail, CC: 0.4 mm (1.6); spleen, CC: 0.9 mm (2.8)). The differences of Dmean associated with inter- and intrafraction motions ranged from − 3.5 to 5.8 Gy for the pancreatic tail and − 1.2 to 3.0 Gy for the spleen. In 6 out of 10 patients, movements of the pancreatic tail and spleen were highlighted as potentially clinically significant because of ≥ 1 Gy dose constraint violation.ConclusionInter- and intrafraction organ motion results into unexpected constrain violations in 60% of a randomly selected neuroblastoma cohort, supporting further prospective exploration of MRgRT.

Malignant Pleural Mesothelioma and Radiotherapy: Lung Toxicity Results of an Interim Analysis in Prospective Pilot Trial

Malignant Pleural Mesothelioma (MPM) is a rare but aggressive intrathoracic malignancy with an overall poor prognosis. Neoadjuvant chemotherapy, surgery and then radiotherapy is the standard of care in early-stage disease. Our study aim is to evaluate the feasibility and toxicity of the novel adjuvant RT in accelerated hypofractionation. We report the lung toxicity preliminary results of the first patients entreated. Starting in 2017, 29 MPM patients were enrolled in the trial (IRST trial 163). All patients were treated with accelerated hypofractionated radiotherapy using a helical 3-D CRT and IMRT system and intensity-modulated arc therapy. We conducted a prospective mono-institutional clinical trial enrolling cyto-histological proven, MPM patients. The major exclusion criteria were: previous thorax radiotherapy, contralateral mediastinum involvement (N3) and/or M1, interstitial pneumopathy, active pneumonitis, and fissural disease. The prescription dose was 30 Gy in five daily fractions, while an inhomogeneous dose escalation to 40 Gy was prescribed based solely upon the presence of gross residual tumor. All patients were treated in a 3-D CRT and IMRT system. Patients underwent functional lung study before to start radiotherapy treatment, 2 months and 6 months after the end of the treatment. The organs at risk dose-volume histograms were converted to a 2-Gy equivalent dose, and we closely adhered to the dose constraints of the literature data. We in particular analyzed lung toxicity of the first 20 patients. No G3/G4 lung toxicity was found. We reported 65.0% G1 pneumonitis and 10% G2 as acute lung toxicity. The majority of the G1 patients had only mild symptoms and pneumonitis was described only for radiologic features with no need for medical therapy. Other respiratory toxicities were G1-G2 cough in 50% of the patients; G1 dyspnea occurred in 65% of the patients and G2 in the 15%. The total lung mean dose was 18 Gy (range 13 Gy-23 Gy), and the contralateral lung mean dose was 2 Gy (range 1 Gy-2 Gy). The median value of Forced Expired Volume in one second (FEV1) recorded was 75.5% (range: 46%-137%) before the treatment was started, the median value of Forced Vital Capacity (FVC) at baseline was 74 (range 46-123) with progressive decreasing values through time. DLCO has also been reported with a progressive decrease over time after radiotherapy treatment. No case of respiratory failure was reported after treatment. Treatment of the intact lung with pleural intensity-modulated arc irradiation is a novel treatment strategy that appears to be safe, feasible, and without a high grade of lung toxicity. More investigations are mandatory. The protocol is ongoing.

Validation of a 2D dose verification systemfor intensity-modulated arc therapy

ObjectiveThe measured dose was shown to be dependent on the angle of beam incidence and influenced by couch absorption when a 2D detector was used in a stationary phantom. The use of a 2D array (MatriXX) in combination with a solid water phantom (RW3) dose verification system was explored, which could take into account the couch absorption influences, generate correction factors (CFs) for each detector element, and also calibrate the measured dose for accurate validation of intensity-modulated arc therapy (IMAT) treatment plans. MethodsBased on the introduction of a homogeneous treatment bed model in the Monaco treatment planning system, CFs(θ) were constructed for all incidence angles using 6 MV photon lines in a 28 cm × 28 cm field for MatriXX at different field incidence angles (0°–360°) as a relative ratio of simulated and measured values. The accuracy of the 2D array in combination with the solid water phantom (MatriXX/RW3) was systematically investigated by verifying 12 IMAT plans with and without CFs. In addition, the resulting assessments were evaluated by 40 additional IMAT plans of different tumor sites, using the COMPASS three-dimensional (3D) dose validation device measurements as a benchmark. ResultsAfter correction based on CFs(θ), the effect of the mean pass rates (3%/3 mm) of the MatriXX 2D array for 12 IMAT plan QA can be seenan explicit improvement of 6.1% was observed with the CFs(θ). The average pass rate increased from 92.0% to 98.1%, and the additional 40 IMAT plans QA γ(3mm/3%) matched well between COMPASS and the measurements for MatriXX/RW3, with CFs(θ)'s of 98.4 ± 1.5 vs. 99.1 ± 0.9 for the phantom plans. For different tumor sites, the cervical, thoracic, and abdominal cases for the 3D COMPASS validation devices were 97.9 ± 1.5 vs. 99.4 ± 0.3, 99.1 ± 0.9 vs. 98.6 ± 1.6, and 98.7 ± 0.9 vs. 99.3 ± 0.7, respectively, with P = 0.051, 0.420, and 0.175. For head tumors, the 2D MatriXX validation pass rate was slightly lower than 3D COMPASS (97.7 ± 2.0 vs. 99.2 ± 0.5, P = 0.048). ConclusionsThe combination of MatriXX with the solid water RW3 phantom and CFs(θ)'s incorporation of the main couch model (iBEAM evo Couchtop EP) proved to be a fast and reliable method for pre-treatment verification of arc therapy with sufficient accuracy. Slight deviations were found for patients with head tumors treated with the treatment bed extension plate assembly iBEAM® evo Extension 415. These could be minimized by constructing the extension plate couch model and then reconstructing the MatriXX/RW3 calibration factor.

Plan Quality Analysis of Automated Treatment Planning Workflow With Commercial Auto-Segmentation Tools and Clinical Knowledge-Based Planning Models for Prostate Cancer.

This study evaluated the feasibility of using artificial intelligence (AI) segmentation software for volume-modulated arc therapy (VMAT) prostate planning in conjunction with knowledge-based planning to facilitate a fully automated workflow. Two commercially available AI software programs, Radformation AutoContour (Radformation, New York, NY) and Siemens AI-Rad Companion (Siemens Healthineers, Malvern, PA) were used to auto-segment the rectum, bladder, femoral heads, and bowel bag on 30 retrospective clinical cases (10 intact prostate, 10 prostate bed, and 10 prostate and lymph node). Physician-segmented target volumes were transferred to AI structure sets. In-house RapidPlan models were used to generate plans using the original, physician-segmented structure sets as well as Radformation and Siemens AI-generated structure sets. Thus, there were three plans for each of the 30 cases, totaling 90 plans. Following RapidPlan optimization, planning target volume (PTV) coverage was set to 95%. Then, the plans optimized using AI structures were recalculated on the physician structure set with fixed monitor units. In this way, physician contours were used as the gold standard for identifying any clinically relevant differences in dose distributions. One-way analysis of variation (ANOVA) was used for statistical analysis. No statistically significant differences were observed across the three sets of plans for intact prostate, prostate bed, or prostate and lymph nodes. The results indicate that an automated volumetric modulated arc therapy (VMAT) prostate planning workflow can consistently achieve high plan quality. However, our results also show that small but consistent differences in contouring preferences may lead to subtle differences in planning results. Therefore, the clinical implementation of auto-contouring should be carefully validated.

Dosimetry study of Auto-VMAT planning and Manual-VMAT planning based on Pinnacle3 9.10 in radiotherapy for cervical cancer.

The purpose of this study was to compare the dose distribution characteristics of automatic volume-modulated arc therapy (Auto-VMAT) planning and manual volume-modulated arc therapy (Manual-VMAT) planning of Philips Pinnacle3 9.10 planning system, to provide a basis for optimal radiation therapy planning for cervical cancer. Ten patients with cervical cancer in our hospital from September to December 2018 were selected, and 2 treatment plans, Auto-VMAT plan and Manual-VMAT plan, were designed using Pinnacle3 9.10 planning system, respectively, to evaluate the maximum dose Dmax, mean dose Dmean, homogeneity index of the target area according to the dose volume histogram, the conformability index, plan optimization time, monitor units (MUs), organ at risk and other indicators. The results were that the Auto-VMAT plan was superior to the Manual-VMAT plan for target area Dmean, conformability index, and homogeneity index, with statistically significant differences (P < .05) and no significant difference in maximum dose Dmax (P > .05); rectal V40, V50, and Dmean in the Auto-VMAT plan, bladder V40, V50, and Dmean, small bowel V30, V40, V50 and Dmean, and right and left femoral V50 and Dmean were all lower than the Manual-VMAT plan, and the difference was statistically significant (P < .05); the mean optimization time for the Auto-VMAT and Manual-VMAT plans was 47 minutes and 35 minutes, respectively, an increase of 34%. The average number of MUs was 519 MUs and 374 MUs, respectively, an increase of 28%. This study concluded that the Pinnacle3 9.10-based Auto-VMAT plan was clinically feasible and significantly superior to the Manual-VMAT plan in terms of improved target area uniformity and conformability and reduced organ endangerment dose while reducing the impact of human factors on the quality of plan design.

Comparative dosimetric and radiobiological assessment of left-sided whole breast and regional nodes with advanced radiotherapy techniques.

The aim of this study was to analyze the dosimetric and radiobiologic differences of the left-sided whole breast and regional nodes in intensity-modulated radiotherapy (IMRT), volume-modulated arc therapy (VMAT), and helical tomotherapy (HT). The IMRT, VMAT, and HT plans in this study were generated for thirty-five left-sided breast cancer patients after breast-conserving surgery (BCS). The planning target volume (PTV) included the whole breast and supraclavicular nodes. PTV coverage, homogeneity index (HI), conformity index (CI), dose to organs at risk (OARs), secondary cancer complication probability (SCCP), and excess absolute risk (EAR) were used to evaluate the plans. Compared to IMRT, the VMAT and HT plans resulted in higher PTV coverage and homogeneity. The VMAT and HT plans also delivered a lower mean dose to the ipsilateral lung (9.19±1.36 Gy, 9.48±1.17 Gy vs. 11.31±1.42 Gy) and heart (3.99±0.86 Gy, 4.48±0.62 Gy vs. 5.53±1.02 Gy) and reduced the V5Gy, V10Gy, V20Gy, V30Gy, and V40Gy of the ipsilateral lung and heart. The SCCP and EAR for the ipsilateral lung were reduced by 3.67%, 3.09% in VMAT, and 22.18%, 19.21% in HT, respectively. While were increased for the contralateral lung and breast. This study showed that VMAT plans provide a more homogeneous dose distribution to the PTV, minimizing exposure to ipsilateral structures and significantly reducing SCCP and EAR, and slightly increasing dose to contralateral structures. Overall, the VMAT plan can be considered a beneficial technique for BCS patients whose PTV includes the whole breast and regional nodes.

Completion surgery after intensity-modulated arc therapy for locally advanced cervical cancer: long-term follow-up and update on surgical outcome and oncologic results of a unique tertiary care single-center retrospective cohort

BackgroundChemoradiotherapy (CRT) followed by brachytherapy (BT) is the standard treatment for locally advanced cervical cancer (LACC), but replacement of BT by surgery (CRT-S) could be an acceptable alternative. The main concern is the risk of operative morbidity. The aim is to report on therapeutic morbidity, OS, PC, and LC of CRT-S.MethodsThis was a single tertiary center retrospective cohort study in patients treated with CRT-S. A type II Wertheim hysterectomy was performed 6–8 weeks after CRT. Acute and chronic radiotherapy-related and surgical morbidity was classified according to the CTCAE v4.0. OS, and DFS, PC, and LC were calculated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard models were performed to determine variables with a prognostic role.ResultsA total of 130 consecutive LACC patients were treated with CRT, and 119 underwent completion surgery. The median follow-up was 53 months. Five-year OS rate, local control, pelvic control, and 5-year DFS rate were 73%, 93%, 90%, and 74%, respectively. The 5-year OS rate was 92%/72%/67%/56% for FIGO (2009) stage I/II/III/IV, respectively. The five-year OS rate was 79% and 71% for adenocarcinoma and squamous cell carcinoma (p > 0.05), respectively. There was no intra- and perioperative mortality. Intraoperative and early postoperative complication rates were 7% and 20% (3% ≥ G3), respectively; they resolved within 3 months. The late postoperative complication rate was 9% (7% ≥ G3). Acute/late radiotherapy-related G3 side effects were 5%/3% for gastrointestinal and 3%/7% for genitourinary side effects.ConclusionsCRT-S is safe with an acceptable rate of complications for both the CRT and completion surgery and shows encouraging outcome data for stage III/IV and adenocarcinoma patients.

Malignant Pleural Mesothelioma: Preliminary Toxicity Results of Adjuvant Radiotherapy Hypofractionation in a Prospective Trial (MESO-RT).

Malignant Pleural Mesothelioma (MPM) is a rare malignancy with an overall poor prognosis. The standard therapeutic strategy in early-stage disease is trimodality therapy. In this publication, we report the preliminary toxicity results of the first 20 patients treated with accelerated hypofractionated radiotherapy. Between July 2017 to June 2019, 20 MPM patients were enrolled and treated with accelerated hypofractionated radiotherapy using helical tomotherapy and intensity-modulated arc therapy. The prescription dose was 30 Gy in five daily fractions, while an inhomogeneous dose escalation to 40 Gy was prescribed based solely upon the presence of gross residual tumor. Only one case of G3 toxicity was reported, which was a bilateral pneumonitis that occurred two years after treatment probably due to superinfection. Median Time to Progression reached 18.2 months while one- and three-year Overall Survival rates were 85% (95% CI:60.4-94.9) and 49.5% (95% CI:26.5-68.9), respectively. Treatment of the intact lung with pleural intensity-modulated arc irradiation is a novel treatment strategy that appears to be safe, feasible, and without a high grade of lung toxicity. Survival rates and Time to Progression are encouraging.

Machine-learning-based prediction of the effectiveness of the delivered dose by exhale-gated radiotherapy for locally advanced lung cancer: The additional value of geometric over dosimetric parameters alone.

This study aimed to assess interfraction stability of the delivered dose distribution by exhale-gated volumetric modulated arc therapy (VMAT) or intensity-modulated arc therapy (IMAT) for lung cancer and to determine dominant prognostic dosimetric and geometric factors. Clinical target volume (CTVPlan) from the planning CT was deformed to the exhale-gated daily CBCT scans to determine CTVi, treated by the respective dose fraction. The equivalent uniform dose of the CTVi was determined by the power law (gEUDi) and cell survival model (EUDiSF) as effectiveness measure for the delivered dose distribution. The following prognostic factors were analyzed: (I) minimum dose within the CTVi (Dmin_i), (II) Hausdorff distance (HDDi) between CTVi and CTVPlan, (III) doses and deformations at the point in CTVPlan at which the global minimum dose over all fractions per patient occurs (PDmin_global_i), and (IV) deformations at the point over all CTVi margins per patient with the largest Hausdorff distance (HDPworst). Prognostic value and generalizability of the prognostic factors were examined using cross-validated random forest or multilayer perceptron neural network (MLP) classifiers. Dose accumulation was performed using back deformation of the dose distribution from CTVi to CTVPlan. Altogether, 218 dose fractions (10 patients) were evaluated. There was a significant interpatient heterogeneity between the distributions of the normalized gEUDi values (p<0.0001, Kruskal-Wallis tests). Accumulated gEUD over all fractions per patient was 1.004-1.023 times of the prescribed dose. Accumulation led to tolerance of ~20% of fractions with gEUDi <93% of the prescribed dose. Normalized Dmin >60% was associated with predicted gEUD values above 95%. Dmin had the highest importance for predicting the gEUD over all analyzed prognostic parameters by out-of-bag loss reduction using the random forest procedure. Cross-validated random forest classifier based on Dmin as the sole input had the largest Pearson correlation coefficient (R=0.897) in comparison to classifiers using additional input variables. The neural network performed better than the random forest classifier, and the gEUD values predicted by the MLP classifier with Dmin as the sole input were correlated with the gEUD values characterized by R=0.933 (95% CI, 0.913-0.948). The performance of the full MLP model with all geometric input parameters was slightly better (R=0.952) than that based on Dmin (p=0.0034, Z-test). Accumulated dose distributions over the treatment series were robust against interfraction CTV deformations using exhale gating and online image guidance. Dmin was the most important parameter for gEUD prediction for a single fraction. All other parameters did not lead to a markedly improved generalizable prediction. Dosimetric information, especially location and value of Dmin within the CTV i , are vital information for image-guided radiation treatment.

Hippocampal Sparing in Stereotactic Radiotherapy for Multiple Brain Metastases: A Comparison of Intensity-modulated Arc Therapy, CyberKnife, and Helical Radiotherapy

Hippocampal Sparing in Stereotactic Radiotherapy for Multiple Brain Metastases: A Comparison of Intensity-modulated Arc Therapy, CyberKnife, and Helical Radiotherapy

High-Dose Brachytherapy in Chemoradiation Schemes of Patients &#x0D; with Oral Mucosa Cancer

The aim of the study was to improve clinical outcomes of oral mucosa cancer in case of surgical treatment failure.Materials and methods. A clinical case of combined radiation treatment of a patient with oral floor mucosa cancer St III T3N1M0 was presented. Pathogistological diagnosis # xxxxxx was: highly differentiated squamous cell carcinoma. A treatment plan was developed. Chemoradiotherapy at the first stage included 3 courses of intra-arterial chemotherapy (Selective (superselective) embolization (chemoembolization) of tumor vessels in the basin of the left and right facial and left lingual arteries, cisplatin 150 mg, combined with a daily infusion of 5-fluorouracil 4000 mg), with an interval 21 day. Chemoradiotherapy at the second stage included volume modulated arc therapy (VMAT) on the area of ​​the primary tumor (oral floor mucosa) and the regional metastasis pathways (total boost dose 60 Gy to the area of ​​regional lymph flow, otal boost dose 50 Gy to the oral cavity). Chemoradiotherapy at stage 3 included interstitial radiation therapy. A single boost dose (SBD) for the primary focus was 3 Gy/per fraction, 2 times a day, with an interval of 6 hours until total boost dose reached 21 Gy, 7 fractions.Results. After treatment, a complete regression of the tumor was noted. No pathological accumulation of radiopharmaceuticals, features of the tumor process was detected on PET/CT 48 months after treatment.Conclusions. Chemoradiotherapy combined with brachytherapy can be considered as an equal alternative to surgical treatment of patients with oral mucosa cancer.

Image Guidance Volume-Modulated Arc Radiation Therapy Concurrently With Nab-Paclitaxel Plus Cisplatin for Patients With Locally Advanced Cervical Cancer: A Single-Arm Dose Escalation Trial

Nanoparticle albumin-bound (nab) paclitaxel has improved uptake by tumor cells in comparison to paclitaxel. The aim of this study was to determine the maximal tolerated dose (MTD) and the dose-limiting toxicity (DLT) of nab-paclitaxel plus cisplatin with concurrent image guidance volume modulated arc therapy for locally advanced cervical cancer (LACC). This single-arm phase 1 trial followed the standard 3+3 dose escalation design. Patients with histologically proven stage IB2-IVA LACC were eligible. Image guidance volume modulated arc therapy included 50.4 Gy in 28 fractions to the pelvis and 59.4 Gy simultaneous boost in 28 fractions to involved pelvic and para-aortic lymph nodes, and subsequent high-dose-rate intracavitary brachytherapy at a total dose of 30.0 Gy in 5 fractions, twice a week. Concurrent chemotherapy regimen included weekly cisplatin (40 mg/m2) and weekly nab-paclitaxel at escalating doses (10, 20, 33, 50, and 70 mg/m2 per week). Duration of the planned treatment was 8 weeks. Grade 4 hematologic toxicity and grade 3 or above nonhematologic toxicity were considered as DLT. MTD was defined as the highest dose with ≤33% DLT. A total of 22 patients were enrolled from September 2019 to August 2021. The most common adverse events were grade 1 to 3 leukopenia, diarrhea, and nausea/vomiting. A total of 4 patients (18.0%) experienced DLT: grade 3 hypokalemia at 33 mg/m2 (1 of 6 subjects), grade 3 deep vein thrombosis at 50 mg/m2 (1 of 6) and 70 mg/m2 (1 of 4), and grade 3 perineum edema at 70 mg/m2 (1 of 3). The estimated MTD was 50 mg/m2. Complete response was observed in 20 patients (90.9%). In patients undergoing concurrent IG-VAMT with nab-paclitaxel plus cisplatin for LACC, MTD of nab-paclitaxel was 50 mg/m2. Complete response rate was 90.9%.

A randomised phase II trial of radiotherapy dose escalation, facilitated by intensity-modulated arc therapy techniques, in high-risk neuroblastoma

<h3>Objectives</h3> This trial compared intensity modulated arc therapy (IMAT) with conventional techniques for high-risk neuroblastoma, to establish whether IMAT could enable a higher radiation dose than standard to be given without exceeding normal tissue dose objectives. The aim was to determine the radiotherapy dose for use in a subsequent international randomised phase III trial. <h3>Methods</h3> Patients were randomised to receive either 21 Gy in 14 fractions, or 36 Gy in 24 fractions. The tumour volume and organs at risk were delineated according to a standard protocol. All patients were dual planned with both conventional and IMAT techniques. A quality assurance team prospectively reviewed the contours and the plans. The better technique, based on planning target volume dose achieved and organ at risk sparing, was selected for use. <h3>Results</h3> From 2017 to 2020, fifty patients were recruited and randomised, 25 to each arm. All 50 patients underwent radiotherapy planning, but only 43 completed protocol treatment, all with the IMAT technique. The IMAT technique improved planning target volume conformity and heterogeneity indices significantly. In the 21 Gy arm, the dose delivered in all patients was 21 Gy. In the 36 Gy arm, the median dose delivered was 36 Gy (range 21 Gy to 36 Gy). Disease progression occurred in 18 patients and 16 patients have died. At two years, the overall survival was 70%, and the event free survival was 60%. This phase II trial was not powered to detect a difference between the arms, and no difference in event-free or overall survival was observed. <h3>Conclusion</h3> This trial confirms that delivery of 36 Gy is possible using an IMAT technique without exceeding normal tissue tolerance. The new SIOPEN High-Risk 2 trial contains a Phase III randomisation comparing 36 Gy with 21.6 Gy inpatients with residual disease after surgery.

Stereotactic Arrhythmia Radioablation in Europe—Treatment Planning Benchmark Results of the STOPSTORM.eu Consortium

<h3>Purpose/Objective(s)</h3> In patients with refractory ventricular tachycardia (VT), Stereotactic Arrhythmia Radioablation (STAR) showed promising results for otherwise untreatable patients. The STOPSTORM.eu project coordinates European efforts to clinically validate STAR and to refine protocols and guidelines. The aim of this work is to present the current clinical STAR practice in Europe based on three examples as baseline for further optimization. <h3>Materials/Methods</h3> Target Volumes (TV) and Organs-at-Risk (OAR) were generated from previous consortium benchmarks and consensus definitions for three well-selected STAR cases. Planning Target Volumes (PTV) were generated based on three different compensation strategies for cardiac and respiratory motion and overlapped/close OARs like coronary arteries or stomach. The STOPSTORM.eu members were asked to generate single fraction treatment plans with 25 Gy dose prescription based on ICRU report 91 for each case based on their STAR clinical practice through multi-disciplinary discussion. Resulting dose distributions were analyzed independently using a customized platform for multi-center treatment planning studies. <h3>Results</h3> By November 2021, 20 centers submitted 22, 23 and 22 treatment plans for case 1, 2 and 3, respectively, mostly (75% of plans) using Intensity Modulated Arc Therapy (IMAT) with 6 MeV FFF beams (73% of the IMAT plans) among other commonly used techniques for stereotactic radiotherapy. Presently, used guidelines for STAR treatment planning and OAR dose limits vary greatly and are mostly based on the AAPM TG-101 report and RAVENTA trial publication. As a major finding, 73% of the submitted plans showed close OAR sparing overachieving high PTV coverage (Figure 1 and Table 1) arguing that lower doses may also result in clinical efficiency. Cases 1 and 3 dose distributions (referenced as A. and C. in Figure 2) highlighted how OARs sparing also resulted in heavy PTV under dosing for some participants. <h3>Conclusion</h3> From this first STOPSTORM.eu multi-center/multi-platform treatment planning benchmark study we obtained important information concerning current clinical practice from major European centers performing Stereotactic Arrhythmia Radioablation for VT. With the strongly varying approaches of the centers as basis, the key task for the STOPSTORM.eu project is to find consensus, aiming to harmonize and optimize STAR practice in Europe.