Organs At Risk Sparing Research Articles

Three-dimensional conformal radiotherapy (3D-CRT) vs. volumetric modulated arc therapy (VMAT) in deep inspiration breath-hold (DIBH) technique in left-sided breast cancer patients-comparative analysis of dose distribution and estimation of projected secondary cancer risk.

The purpose of this study was to compare two techniques of irradiation of left-sided breast cancer patients who underwent breast-conserving surgery, three-dimensional conformal radiotherapy technique (3D-CRT) and volumetric modulated arc therapy (VMAT), in terms of dose distribution in the planning target volume (PTV) and organs at risk (OARs). The second aim of the study was estimation of the projected risk of radiation-induced secondary cancer for both radiotherapy techniques. For 25patients who underwent CT simulation in deep inspiration breath-hold (DIBH), three treatment plans were generated: one using athree-dimensional conformal radiotherapy technique and two using volumetric modulated arc therapy. First VMAT-DIBH geometry consisted of three partial arcs (ARC-DIBH 3A) and second consisted of four partial arcs (ARC-DIBH 4A). Cumulative dose-volume histograms (DVHs) were used to compare dose distributions within the PTV and OARs (heart, left anterior descending coronary artery [LAD], ipsilateral and contralateral lung [IL, CL], and contralateral breast [CB]). Normal tissue complication probabilities (NTCPs) and organ equivalent doses (OEDs) were calculated using the differential DVHs. Excess absolute risks (EARs) for second cancers were estimated using Schneider's full mechanistic dose-response model. All plans fulfilled the criterium for PTV V95% ≥ 95%. The PTV coverage, homogeneity, and conformity indices were significantly better for VMAT-DIBH. VMAT showed asignificantly increased mean dose and V5Gy for all OARs, but reduced LAD Dmax by 15 Gy. For IL, CL, and CB, the 3D-CRT DIBH method achieved the lowest values of EAR: 28.38 per 10,000PYs, 2.55 per 10,000PYs, and 4.48 per 10,000PYs (p < 0.001), compared to 40.29 per 10,000PYs, 15.62 per 10,000PYs, and 23.44 per 10,000PYs for ARC-DIBH 3A plans and 41.12 per 10,000PYs, 15.59 per 10,000PYs, and 22.73 per 10,000PYs for ARC-DIBH 4A plans. Both techniques provided negligibly low NTCPs for all OARs. The study shows that VMAT-DIBH provides better OAR sparing against high doses. However, the large low-dose-bath (≤ 5 Gy) is still aconcern due to the fact that alarger volume of normal tissues exposed to lower doses may increase aradiation-induced risk of secondary cancer.

Organ-at-risk sparing with dynamic trajectory radiotherapy for head and neck cancer: comparison with volumetric arc therapy on a publicly available library of cases

BackgroundDynamic trajectory radiotherapy (DTRT) extends volumetric modulated arc therapy (VMAT) with dynamic table and collimator rotation during beam-on. The aim of the study is to establish DTRT path-finding strategies, demonstrate deliverability and dosimetric accuracy and compare DTRT to state-of-the-art VMAT for common head and neck (HN) cancer cases.MethodsA publicly available library of seven HN cases was created on an anthropomorphic phantom with all relevant organs-at-risk (OARs) delineated. DTRT plans were generated with beam incidences minimizing fractional target/OAR volume overlap and compared to VMAT. Deliverability and dosimetric validation was carried out on the phantom.ResultsDTRT and VMAT had similar target coverage. For three locoregionally advanced oropharyngeal carcinomas and one adenoid cystic carcinoma, mean dose to the contralateral salivary glands, pharynx and oral cavity was reduced by 2.5, 1.7 and 3.1 Gy respectively on average with DTRT compared to VMAT. For a locally recurrent nasopharyngeal carcinoma, D0.03 cc to the ipsilateral optic nerve was above tolerance (54.0 Gy) for VMAT (54.8 Gy) but within tolerance for DTRT (53.3 Gy). For a laryngeal carcinoma, DTRT resulted in higher dose than VMAT to the pharynx and brachial plexus but lower dose to the upper oesophagus, thyroid gland and contralateral carotid artery. For a single vocal cord irradiation case, DTRT spared most OARs better than VMAT. All plans were delivered successfully on the phantom and dosimetric validation resulted in gamma passing rates of 93.9% and 95.8% (2%/2 mm criteria, 10% dose threshold).ConclusionsThis study provides a proof of principle of DTRT for common HN cases with plans that were deliverable on a C-arm linac with high accuracy. The comparison with VMAT indicates substantial OAR sparing could be achieved.

Ways to unravel the clinical potential of carbon ions for head and neck cancer reirradiation: dosimetric comparison and local failure pattern analysis as part of the prospective randomized CARE trial

BackgroundCarbon ion radiotherapy (CIRT) yields biophysical advantages compared to photons but randomized studies for the reirradiation setting are pending. The aim of the current project was to evaluate potential clinical benefits and drawbacks of CIRT compared to volumetric modulated arc therapy (VMAT) in recurrent head and neck cancer.MethodsDose-volume parameters and local failure patterns of CIRT compared to VMAT were evaluate in 16 patients from the randomized CARE trial on head and neck cancer reirradiation.ResultsDespite an increased target dose, CIRT resulted in significantly reduced organ at risk (OAR) dose across all patients (− 8.7% Dmean). The dose-volume benefits were most pronounced in the brainstem (− 20.7% Dmax) and the optic chiasma (− 13.0% Dmax). The most frequent local failure was type E (extraneous; 50%), followed type B (peripheral; 33%) and type A (central; 17%). In one patient with type A biological and/or dosimetric failure after CIRT, mMKM dose recalculation revealed reduced target coverage.ConclusionsCIRT resulted in highly improved critical OAR sparing compared to VMAT across all head and neck cancer reirradiation scenarios despite an increased prescription dose. Local failure pattern analysis revealed further potential CIRT specific clinical benefits and potential pitfalls with regard to image-guidance and biological dose-optimization.

COMPARISON OF COPLANAR AND NON- COPLANARVMAT FOR BRAIN CANCER BY USING THE DOSIMETRICAL AND RADIOBIOLOGICAL INDICES

Background: Recent techniques of radiotherapy such as volumetric modulated arc therapy (VMAT) that delivered in Coplanar technique or non-coplanar technique allows to deliver high doses to the brain tumors, at the same time reducing the risk of normal tissues as compared with intensity modulated radiotherapy (IMRT) and the three-dimensional conformal radiotherapy (3D-CRT). Aim: The aim of the current work is to compare dosimetrical and radiobiological indices of treatment plans for brain tumor using CO-VMAT and NC-VMAT techniques to choose the optimum technique for the treated cases. Patients and methods: Twenty-one cases with brain tumors were performed for the treatment planning study. The cases are planned by using the coplanar and non coplanar VMAT techniques and optimized to evaluate and compare dosimetrical and radiobiological parameters related to PTV dose coverage and sparing of organs at risk. The total dose of CO-VMAT and NC-VMAT plans is 60 Gray in 30 fractions during a single phase with a daily dose of 2 Gray. Results: In dosimetrical calculations, CO-VMAT and NC-VMAT techniques gave similar (homogeneity index HI, modified homogeneity index MHI, conformity index CI and quality factor QF) values for the PTV, while CO-VMAT was the higher in (target coverage index TCI, prescription isodose to target volume ratio PITV and conformity number CN) values and the lower in (gradient index GI, gradient measure GM) values, and NC-VMAT was the lower in Monitor units MUs values. In radiobiological calculations, equivalent uniform dose EUD values, tumor control probability TCP and complication free tumor control probability P+ were large in CO-VMAT and normal tissue complication probability NTCP was less in NC-VMAT. Conclusion: While the previous studies showed that CO-VMAT technique was used when the tumor is far from the organs at risk, the present work found CO-VMAT can be used when the tumor is near to or far from organs at risk (OARs) because it can achieve the target dose coverage and sparing of OARs together. We strongly recommend that NC-VMAT technique should be used when the OARs are located inside the tumor to be able to achieve more sparing of them.

Evaluation of the dosimetric and radiobiological parameters in four radiotherapy regimens for synchronous bilateral breast cancer.

This study is to investigate the optimal treatment option for synchronous bilateral breast cancer (SBBC) by comparing dosimetric and radiobiological parameters of intensity‐modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) plans using single and dual isocenters.Twenty patients with SBBC without lymph node involvement were selected retrospectively. Four treatment plans were generated for each patient using the Eclipse treatment planning system (Varian Medical System, Palo Alto, CA, USA) following two delivery techniques with two isocenter conditions—IMRT using a single isocenter (IMRT_Iso1), VMAT using a single isocenter (VMAT_Iso1), IMRT using dual isocenters (IMRT_Iso2), and VMAT using dual isocenters (VMAT_Iso2). A dose of 42.56 Gy in 16 fractions was prescribed for the planning target volume (PTV). All plans were calculated using the Acuros XB algorithm and a photon optimizer for a 6‐MV beam of a Vital Beam linear accelerator. PTV‐related dosimetric parameters were analyzed. Further, the homogeneity index, conformity index, and conformation number were computed to evaluate plan quality. Dosimetric parameters were also measured for the organs at risk (OARs). In addition, the equivalent uniform dose corresponding to an equivalent dose related to a reference of 2 Gy per fraction, the tumor control probability, and the normal tissue complication probability were calculated based on the dose–volume histogram to investigate the radiobiological impact on PTV and OARs.IMRT_Iso1 exhibited similar target coverage and a certain degree of dosimetric improvement in OAR sparing compared to the other techniques. It also exhibited some radiobiological improvement, albeit insignificant. Although IMRT_Iso1 significantly increased monitor unit compared to VMAT_Iso1, which is the best option in terms of delivery efficiency, there was only a 22% increase in delivery time. Therefore, in conclusion, IMRT_Iso1, the complete treatment of which can be completed using a single setup, is the most effective method for treating SBBC.

Target Definition in MR-Guided Adaptive Radiotherapy for Head and Neck Cancer.

Simple SummaryAdaptive radiotherapy for head and neck cancer has become more routine due to an increase in imaging quality and improvement in radiation techniques. With the availability of faster adaptive workflows, it is possible to adapt more easily to (daily) changes. MRI offers besides great anatomical imaging, also functional information about the tumor and surrounding tissue. The aim of this review is to provide current state of evidence about target definition on MRI for adaptive strategies in the treatment of head and neck cancer.In recent years, MRI-guided radiotherapy (MRgRT) has taken an increasingly important position in image-guided radiotherapy (IGRT). Magnetic resonance imaging (MRI) offers superior soft tissue contrast in anatomical imaging compared to computed tomography (CT), but also provides functional and dynamic information with selected sequences. Due to these benefits, in current clinical practice, MRI is already used for target delineation and response assessment in patients with head and neck squamous cell carcinoma (HNSCC). Because of the close proximity of target areas and radiosensitive organs at risk (OARs) during HNSCC treatment, MRgRT could provide a more accurate treatment in which OARs receive less radiation dose. With the introduction of several new radiotherapy techniques (i.e., adaptive MRgRT, proton therapy, adaptive cone beam computed tomography (CBCT) RT, (daily) adaptive radiotherapy ensures radiation dose is accurately delivered to the target areas. With the integration of a daily adaptive workflow, interfraction changes have become visible, which allows regular and fast adaptation of target areas. In proton therapy, adaptation is even more important in order to obtain high quality dosimetry, due to its susceptibility for density differences in relation to the range uncertainty of the protons. The question is which adaptations during radiotherapy treatment are oncology safe and at the same time provide better sparing of OARs. For an optimal use of all these new tools there is an urgent need for an update of the target definitions in case of adaptive treatment for HNSCC. This review will provide current state of evidence regarding adaptive target definition using MR during radiotherapy for HNSCC. Additionally, future perspectives for adaptive MR-guided radiotherapy will be discussed.

Impact of Using Unedited CT-Based DIR-Propagated Autocontours on Online ART for Pancreatic SBRT.

PurposeTo determine the dosimetric impact of using unedited autocontours in daily plan adaptation of patients with locally advanced pancreatic cancer (LAPC) treated with stereotactic body radiotherapy using tumor tracking.Materials and MethodsThe study included 98 daily CT scans of 35 LAPC patients. All scans were manually contoured (MAN), and included the PTV and main organs-at-risk (OAR): stomach, duodenum and bowel. Precision and MIM deformable image registration (DIR) methods followed by contour propagation were used to generate autocontour sets on the daily CT scans. Autocontours remained unedited, and were compared to MAN on the whole organs and at 3, 1 and 0.5 cm from the PTV. Manual and autocontoured OAR were used to generate daily plans using the VOLO™ optimizer, and were compared to non-adapted plans. Resulting planned doses were compared based on PTV coverage and OAR dose-constraints.ResultsOverall, both algorithms reported a high agreement between unclipped MAN and autocontours, but showed worse results when being evaluated on the clipped structures at 1 cm and 0.5 cm from the PTV. Replanning with unedited autocontours resulted in better OAR sparing than non-adapted plans for 95% and 84% plans optimized using Precision and MIM autocontours, respectively, and obeyed OAR constraints in 64% and 56% of replans.ConclusionFor the majority of fractions, manual correction of autocontours could be avoided or be limited to the region closest to the PTV. This practice could further reduce the overall timings of adaptive radiotherapy workflows for patients with LAPC.

Stereotactic arrhythmia radioablation in europe: treatment planning benchmark results of the STOPSTORM consortium

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): EU Background In patients with refractory ventricular tachycardia (VT), STereotactic Arrhythmia Radioablation (STAR) showed promising results for otherwise untreatable patients [1]. The STOPSTORM.eu project coordinates European efforts to clinically validate STAR and to refine protocols and guidelines to ensure treatment harmonization. Purpose The aim of this work is to present the current clinical STAR practise in Europe based on three examples as baseline for further optimization. Methods Target Volumes (TV) and Organs-at-Risk (OAR) were generated from previous consortium benchmarks and consensus definitions for three well-selected STAR cases [1]. Planning Target Volumes (PTV) were generated based on three different compensation strategies for cardiac and respiratory motion [2] and overlapped close OAR like coronary arteries or stomach in some areas. 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 clinical practise and preferences for STAR including multi-disciplinary discussion and plan approval. Resulting dose distributions were analysed independently using a customized platform for multi-center treatment planning studies [3]. Results Twenty centers submitted 22, 23 and 22 treatment plans for case 1, 2 and 3, respectively, mostly (75% of all 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. At this current stage, used guidelines for STAR treatment planning and OAR dose limits vary greatly and are mostly based on the AAPM TG-101 report or the RAVENTA trial publication [4]. As a major finding, 73% of all plans submitted preferred close OAR sparing over achieving high PTV coverage arguing that lower doses down to 20 Gy may also result in clinical efficiency as recently suggested [5]. As a minor finding, 80% of the centers chose to override strong artifact regions originating from e.g. left ventricular assist devices. Conclusion From this first STOPSTORM.eu multi-center multi-platform treatment planning benchmark study we obtained important information concerning current clinical preference and practise from major European centers performing STereotactic Arrhythmia Radioablation for VT. Using the individual and strongly varying approaches of the centers, the key task for the STOPSTORM.eu project is now to find consensus in order to harmonize and optimize STAR practise in Europe.

Range uncertainty reductions in proton therapy may lead to the feasibility of novel beam arrangements which improve organ-at-risk sparing.

In proton therapy, dose distributions are currently often conformed to organs at risk (OARs) using the less sharp dose fall-off at the lateral beam edge to reduce the effects of uncertainties in the in vivo proton range. However, range uncertainty reductions may make greater use of the sharper dose fall-off at the distal beam edge feasible, potentially improving OAR sparing. We quantified thebenefits of such novel beam arrangements. For each of 10 brain or skull base cases, five treatment plans robust to 2mm setup and 0%-4% range uncertainty were created for the traditional clinical beam arrangement and a novel beam arrangement making greater use of the distal beam edge to conform the dose distribution to the brainstem. Metrics including the brainstem normal tissue complication probability (NTCP) with the endpoint of necrosis were determined for all plans and all setup and range uncertainty scenarios. For the traditional beam arrangement, reducing the range uncertainty from the current level of approximately 4% to a potentially achievable level of 1% reduced the brainstem NTCP by up to 0.9 percentage points in the nominal and up to 1.5 percentage points in the worst-case scenario. Switching to the novel beam arrangement at 1% range uncertainty improved these values by a factor of 2, that is, to 1.8 percentage points and 3.2 percentage points, respectively. The novel beam arrangement achieved a lower brainstem NTCP in all cases starting at a range uncertainty of 2%. The benefits of novel beam arrangements may be of the same magnitude or even exceed the direct benefits of range uncertainty reductions. Indirect effects may therefore contribute markedly to the benefits of reducing proton range uncertainties.

Investigation of Isotoxic Dose Escalation and Plan Quality with TDABC Analysis on a 0.35 T MR-Linac (MRL) System in Ablative 5-Fraction Stereotactic Magnetic Resonance-Guided Radiation Therapy (MRgRT) for Primary Pancreatic Cancer.

This study investigates plan quality generated by an MR-Linac (MRL) treatment planning system (TPS) for 5-fraction stereotactic body radiation therapy (SBRT) of primary pancreatic cancer (PCa). In addition, an isotoxic dose escalation was investigated with the MRL TPS based on stereotactic MR-guided adaptive radiation therapy (SMART) trial constraints. A clinical workflow was developed for adaptive and non-adaptive treatments with the MRL, on which a time-driven activity-based costing (TDABC) analysis was performed to quantify clinical efficacy. Fifteen PCa patients previously treated with a conventional Linac were retrospectively re-planned for this study. Three plans were generated for each patient using the original prescription dose (PD) and organ at risk (OAR) constraints (Plan 1), following SMART trial’s OAR constraints but with the original PD (Plan 2), starting with Plan 2, following an isotoxic dose escalation strategy where the dose was escalated until any one of the SMART trial’s OAR constraints reached its limit (Plan 3). Conformity index (CI) and the ratio of the 50% isodose volume to PTV (R50%) conformity metrics were calculated for all 45 MRL plans, in addition to standard dose-volume indices. Forty-five MRL plans were created which met their respective dosimetric criteria described above. For Plan 1, the MRL TPS successfully achieved equivalent or lower OAR doses while maintaining the prescribed PTV coverage for the 15 plans. A maximum dose to the small bowel was reduced on average by 4.97 Gy (range: 1.11–10.58 Gy). For Plan 2, the MRL TPS successfully met all SMART trial OAR constraints while maintaining equivalent PTV coverage. For Plan 3, the MRL TPS was able to escalate the prescription dose from the original 25–33 Gy by, on average, 36 Gy (range: 15–70 Gy), and dose to the PTV was successfully escalated to at least 50 Gy for all 15 plans. These achievements were made possible, in part, due to the omission of the ITV afforded by the MRL’s real-time target tracking technology and sharper dose penumbra due to its unique dual-focus MLC design. The 0.35T MRL TPS can generate plans that are equivalent to conventional Linac-based plans for SBRT of PCa. Through analyzing Plan 2 and 3 strategies, and due to the real-time target localization capabilities of the MRL system, increased OAR sparing and/or target dose escalation are possible.

Optimizing the Beam Selection for Noncoplanar VMAT by Using Simulated Annealing Approach

Noncoplanar volumetric modulated arc therapy (VMAT) treatment can achieve better organ-at-risk (OAR) avoidance by orienting the radiation beams in a different geometric plane relative to the patient. However, determining the optimal set of beam orientations is challenging due to the additional degrees of freedom. The objective of this study was to use simulated annealing (SA) for beam selection in a noncoplanar VMAT optimization context. The SA method was combined with a direct leaf trajectory optimization approach to obtain a set of globally optimal beams which serve as control points for the treatment trajectory. The proposed method was evaluated through the TG119 benchmark and two clinical cases (prostate and liver cancers). Finally, the SA beam selection method was compared to the standard coplanar and noncoplanar beam selection approaches. The results showed an accurate delivery of the prescription dose to the target tumor volume in all cases. Generally, not on every organ, the noncoplanar SA method showed better OAR sparing compared to the coplanar and noncoplanar greedy method. This work demonstrates that optimized noncoplanar beam orientations using the proposed SA method can be more clinically interesting than the coplanar method in some specific patient cases.

Evaluation of an automated template-based treatment planning system for radiotherapy of anal, rectal and prostate cancer.

The Ethos system has enabled online adaptive radiotherapy (oART) by implementing an automated treatment planning system (aTPS) for both intensity-modulated radiotherapy (IMRT) and volumetric modulated arc radiotherapy (VMAT) plan creation. The purpose of this study is to evaluate the quality of aTPS plans in the pelvic region. Sixty patients with anal (n=20), rectal (n=20) or prostate (n=20) cancer were retrospectively re-planned with the aTPS. Three IMRT (7-, 9- and 12-field) and two VMAT (2 and 3 arc) automatically generated plans (APs) were created per patient. The duration of the automated plan generation was registered. The best IMRT-AP and VMAT-AP for each patient were selected based on target coverage and dose to organs at risk (OARs). The AP quality was analyzed and compared to corresponding clinically accepted and manually generated VMAT plans (MPs) using several clinically relevant dose metrics. Calculation-based pre-treatment plan quality assurance (QA) was performed for all plans. The median total duration to generate the five APs with the aTPS was 55min, 39min and 35min for anal, prostate and rectal plans, respectively. The target coverage and the OAR sparing were equivalent for IMRT-APs and VMAT-MPs, while VMAT-Aps.demonstrated lower target dose homogeneity and higher dose to some OARs. Both conformity and homogeneity index were equivalent (rectal) or better (anal and prostate) for IMRT-APs compared to VMAT-MPs. All plans passed the patient-specific QA tolerance limit. The aTPS generates plans comparable to MPs within a short time-frame which is highly relevant for oART treatments.

MR-Guided Adaptive Radiotherapy for OAR Sparing in Head and Neck Cancers

Simple SummaryNormal tissue toxicities in head and neck cancer persist as a cause of decreased quality of life and are associated with poorer treatment outcomes. The aim of this article is to review organ at risk (OAR) sparing approaches available in MR-guided adaptive radiotherapy and present future developments which hope to improve treatment outcomes. Increasing the spatial conformity of dose distributions in radiotherapy is an important first step in reducing normal tissue toxicities, and MR-guided treatment devices presents a new opportunity to use biological information to drive treatment decisions on a personalized basis.MR-linac devices offer the potential for advancements in radiotherapy (RT) treatment of head and neck cancer (HNC) by using daily MR imaging performed at the time and setup of treatment delivery. This article aims to present a review of current adaptive RT (ART) methods on MR-Linac devices directed towards the sparing of organs at risk (OAR) and a view of future adaptive techniques seeking to improve the therapeutic ratio. This ratio expresses the relationship between the probability of tumor control and the probability of normal tissue damage and is thus an important conceptual metric of success in the sparing of OARs. Increasing spatial conformity of dose distributions to target volume and OARs is an initial step in achieving therapeutic improvements, followed by the use of imaging and clinical biomarkers to inform the clinical decision-making process in an ART paradigm. Pre-clinical and clinical findings support the incorporation of biomarkers into ART protocols and investment into further research to explore imaging biomarkers by taking advantage of the daily MR imaging workflow. A coherent understanding of this road map for RT in HNC is critical for directing future research efforts related to sparing OARs using image-guided radiotherapy (IGRT).

Dosimetric and radiobiological comparison of simultaneous integrated boost radiotherapy for early stage right side breast cancer between three techniques: IMRT, hybrid IMRT and hybrid VMAT

PurposeThis study aimed at evaluating the clinical impact of full intensity-modulated radiotherapy (IMRT), hybrid IMRT (H-IMRT) and hybrid volumetric-modulated arc therapy (H-VMAT) for early-stage breast cancer with simultaneous integrated boost (SIB), in terms of plan quality and second cancer risk (SCR).MethodsThree different plans were designed in full IMRT, hybrid IMRT, and hybrid VMAT for each of twenty patients with early-stage breast cancer. Target quality, organs at risk (OARs) sparing, and SCR were compared among the three plans for each case.ResultsIn compared with H-IMRT, IMRT plans showed deterioration in terms of D2% of SIB, V10 of ipsilateral lung, and excess absolute risk (EAR) to contralateral lung (C-Lung) and esophagus. D2% and the homogeneity index (HI) of SIB, V5 of ipsilateral lung (I-Lung), the Dmean of the esophagus, the EAR to C-Lung and the esophagus with hybrid VMAT dramatically increased by 0.63%, 10%, 17.99%, 149.27%, 230.41%, and 135.29%, respectively (p = 0.024; 0.025; 0.046; 0.011; 0.000; 0.014). Dmean of the heart, the EAR to contralateral breast (C-Breast) and C-Lung by full IMRT was significantly decreased in comparison to the H-VMAT (4.67%, p = 0.033, 26.76%, p = 0.018; 48.05%, p = 0.036).ConclusionThe results confirmed that H-IMRT could achieve better target quality and OARs sparing than IMRT and H-VMAT for SIB radiotherapy of early-stage right breast cancer. H-IMRT was the best treatment option, while H-VMAT performed the worst among the three plans in terms of SCR to peripheral OARs.

Induction chemotherapy followed by radical chemoradiotherapy for patients with stage IV non-metastatic nasopharyngeal carcinoma: 11-Year Experience in a tertiary centre.

T4 nasopharyngeal carcinoma (NPC) with close proximity to critical organs at risk (OARs) is usually underdosed during radiotherapy in order to respect radiation constraints. N3 disease has high risk of distant metastasis. Induction chemotherapy (IC) provides advantages of sparing of OARs during subsequent chemoradiotherapy (CCRT) and early eradication of micrometastasis. However, factors predicting successes of IC in this patient group are not well-studied. 104 T4 or N3 NPC patients were retrospectively reviewed during 2007-2018. They were planned for IC followed by CCRT using intensity-modulated radiotherapy. In the whole group, five-year failure-free survival (FFS), locoregional failure-free survival (LRFS), distant failure-free survival (DFFS) and overall survival (OS) were 40.9%, 45.7%, 46.9% and 53.6% respectively. Isolated marginal failure rate was 5% (4/80) among patients with primary tumours located close to critical OARs. Pre-IC gross tumour volume primary (GTVp) total volume > 110 cm3 correlated with worse five-year LRFS (OR 6.37, P = 0.008), DFFS (OR 8.89, P = 0.003) and OS (OR 50.12, P < 0.001). In the T4 subgroup, IC improved D100% GTVp from 61.39 Gy to 64.71 Gy (P < 0.001) and V100% GTVp from 98.78% to 99.28% (P < 0.001). Our study demonstrated improved dosimetric parameters and low isolated marginal failure rate. It supported the use of IC and CCRT for tumours located close to critical OARs. Further research is warranted to compare predictive roles of pre- and post-IC tumour volumes. For high-risk patients being defined by pre-IC volume or other prognostic models, treatment escalation should be considered.

Dosimetric benefit of MR-guided online adaptive radiotherapy in different tumor entities: liver, lung, abdominal lymph nodes, pancreas and prostate

BackgroundHybrid magnetic resonance (MR)-Linac systems have recently been introduced into clinical practice. The systems allow online adaption of the treatment plan with the aim of compensating for interfractional anatomical changes. The aim of this study was to evaluate the dose volume histogram (DVH)-based dosimetric benefits of online adaptive MR-guided radiotherapy (oMRgRT) across different tumor entities and to investigate which subgroup of plans improved the most from adaption.MethodsFifty patients treated with oMRgRT for five different tumor entities (liver, lung, multiple abdominal lymph nodes, pancreas, and prostate) were included in this retrospective analysis. Various target volume (gross tumor volume GTV, clinical target volume CTV, and planning target volume PTV) and organs at risk (OAR) related DVH parameters were compared between the dose distributions before and after plan adaption.ResultsAll subgroups clearly benefited from online plan adaption in terms of improved PTV coverage. For the liver, lung and abdominal lymph nodes cases, a consistent improvement in GTV coverage was found, while many fractions of the prostate subgroup showed acceptable CTV coverage even before plan adaption. The largest median improvements in GTV near-minimum dose (D98%) were found for the liver (6.3%, p < 0.001), lung (3.9%, p < 0.001), and abdominal lymph nodes (6.8%, p < 0.001) subgroups. Regarding OAR sparing, the largest median OAR dose reduction during plan adaption was found for the pancreas subgroup (-87.0%). However, in the pancreas subgroup an optimal GTV coverage was not always achieved because sparing of OARs was prioritized.ConclusionWith online plan adaptation, it was possible to achieve significant improvements in target volume coverage and OAR sparing for various tumor entities and account for interfractional anatomical changes.

Optimized Conformal Total Body Irradiation methods with Helical TomoTherapy and Elekta VMAT: Implementation, Imaging, Planning and Dose Delivery for Pediatric Patients.

Optimized conformal total body irradiation (OC-TBI) is a highly conformal image guided method for irradiating the whole human body while sparing the selected organs at risk (OARs) (lungs, kidneys, lens). This study investigated the safety and feasibility of pediatric OC-TBI with the helical TomoTherapy (TomoTherapy) and volumetric modulated arc (VMAT) modalities and their implementation in routine clinical practice. This is the first study comparing the TomoTherapy and VMAT modalities in terms of treatment planning, dose delivery accuracy, and toxicity for OC-TBI in a single-center setting. The OC-TBI method with standardized dosimetric criteria was developed and implemented with TomoTherapy. The same OC-TBI approach was applied for VMAT. Standardized treatment steps, namely, positioning and immobilization, contouring, treatment planning strategy, plan evaluation, quality assurance, visualization and treatment delivery procedure were implemented for 157 patients treated with TomoTherapy and 52 patients treated with VMAT. Both modalities showed acceptable quality of the planned target volume dose coverage with simultaneous OARs sparing. The homogeneity of target irradiation was superior for TomoTherapy. Overall assessment of the OC-TBI dose delivery was performed for 30 patients treated with VMAT and 30 patients treated with TomoTherapy. The planned and delivered (sum of doses for all fractions) doses were compared for the two modalities in groups of patients with different heights. The near maximum dose values of the lungs and kidneys showed the most significant variation between the planned and delivered doses for both modalities. Differences in the patient size did not result in statistically significant differences for most of the investigated parameters in either the TomoTherapy or VMAT modality. TomoTherapy-based OC-TBI showed lower variations between planned and delivered doses, was less time-consuming and was easier to implement in routine practice than VMAT. We did not observe significant differences in acute and subacute toxicity between TomoTherapy and VMAT groups. The late toxicity from kidneys and lungs was not found during the 2.3 years follow up period. The study demonstrates that both modalities are feasible, safe and show acceptable toxicity. The standardized approaches allowed us to implement pediatric OC-TBI in routine clinical practice.

Stereotactic MR-Guided Radiotherapy for Pancreatic Tumors: Dosimetric Benefit of Adaptation and First Clinical Results in a Prospective Registry Study.

IntroductionStereotactic MR-guided adaptive radiotherapy (SMART) is an attractive modality of radiotherapy for pancreatic tumors. The objectives of this prospective registry study were to report the dosimetric benefits of daily adaptation of SMART and the first clinical results in pancreatic tumors.Materials and MethodsAll patients treated in our center with SMART for a pancreatic tumor were included. Patients were planned for five daily-adapted fractions on consecutive days. Endpoints were acute toxicities, late toxicities, impact of adaptive treatment on target volume coverage and organs at risk (OAR) sparing, local control (LC) rate, distant metastasis-free survival (DMFS), and overall survival (OS).ResultsThirty consecutive patients were included between October 2019 and April 2021. The median dose prescription was 50 Gy. No patient presented grade > 2 acute toxicities. The most frequent grade 1–2 toxicities were asthenia (40%), abdominal pain (40%), and nausea (43%). Daily adaptation significantly improved planning target volume (PTV) and gross tumor volume (GTV) coverage and OAR sparing. With a median follow-up of 9.7 months, the median OS, 6-month OS, and 1-year OS were 14.1 months, 89% (95% CI: 70%–96%), and 75% (95% CI: 51%–88%), respectively, from SMART completion. LC at 6 months and 1 year was respectively 97% (95% CI: 79–99.5%) and 86% (95% CI: 61%–95%). There were no grade > 2 late toxicities. With a median follow-up of 10.64 months, locally advanced pancreatic cancer (LAPC) and borderline resectable pancreatic cancer (BRPC) patients (22 patients) had a median OS, 6-month OS, and 1-year OS from SMART completion of 14.1 months, 76% (95% CI: 51%–89%), and 70% (95% CI: 45%–85%), respectively. Nine patients underwent surgical resection (42.1% of patients with initial LAPC and 33.3% of patients with BRPC), with negative margins (R0). Resected patients had a significantly better OS as compared to unresected patients (p = 0.0219, hazard ratio (HR) = 5.78 (95% CI: 1.29–25.9)).ConclusionSMART for pancreatic tumors is feasible without limiting toxicities. Daily adaptation demonstrated a benefit for tumor coverage and OAR sparing. The severity of observed acute and late toxicities was low. OS and LC rates were promising. SMART achieved a high secondary resection rate in LAPC patients. Surgery after SMART seemed to be feasible and might increase OS in these patients.

Dosimetric comparison of complete block in ovarian protection between helical tomotherapy and volumetric-modulated arc therapy for cervical cancer

This study is aimed at comparing the dosimetric differences of restricting beamlets passing in protecting ovaries between helical tomotherapy (HT) and volumetric-modulated arc therapy (VMAT) for patients with cervical cancer, and particularly comparing the γ passing rates of ovaries between the two techniques by independent dose calculations. 15 patients with cervical cancer who had undergone ovarian transposition were randomly enrolled. The HT and VMAT plans were created for each involved patient. Target quality, organs at risk (OARs) sparing, and γ passing rates of ovaries were compared between HT and VMAT. HT achieved better than VMAT in D98%, D2%, Dmean, conformal index and homogeneity index (P < 0.05). Almost all OARs in HT had lower radiation dose than those in VMAT (P < 0.05). All the γ passing rates of the ovaries were 100% for the 15 patients both in HT and VMAT. The results suggests that HT outperforms VMAT in terms of target coverage and OARs sparing. Although the calculated dose to the ovaries was accurate both in HT and VMAT, HT showed further advantages for cervical cancer patients with ovarian protection requirements.

Improved healthy tissue sparing in proton therapy of lung tumors using statistically sound robust optimization and evaluation

IntroductionRobust planning is essential in proton therapy for ensuring adequate treatment delivery in the presence of uncertainties. For both robust optimization and evaluation, commonly-used techniques can be overly conservative in selecting error scenarios and lack in providing quantified confidence levels. In this study, established techniques are compared to comprehensive alternatives to assess the differences in target coverage and organ at risk (OAR) dose. MethodThirteen lung cancer patients were planned. Two robust optimization methods were used: scenario selection from marginal probabilities (SSMP) based on using maximum setup and range error values and scenario selection from joint probabilities (SSJP) that selects errors on a predefined 90% hypersurface. Two robust evaluation methods were used: conventional evaluation (CE) based on generating error scenarios from combinations of maximum errors of each uncertainty source and statistical evaluation (SE) via the Monte Carlo dose engine MCsquare which considers scenario probabilities. ResultsPlans optimized using SSJP had, on average, 0.5 Gy lower dose in CTV D98(worst-case) than SSMP-optimized plans. When evaluated using SE, 92.3% of patients passed our clinical threshold in both optimization methods. Average gains in OAR sparing were recorded when transitioning from SSMP to SSJP: esophagus (0.6 Gy D2(nominal), 0.9 Gy D2(worst-case)), spinal cord (3.9 Gy D2(nominal), 4.1 Gy D2(worst-case)) heart (1.1 Gy Dmean, 1.9% V30), lungs-GTV (1.0 Gy Dmean , 1.9% V30). ConclusionOptimization using SSJP yielded significant OAR sparing in all recorded metrics with a target robustness within our clinical objectives, provided that a more statistically sound robustness evaluation method was used.