Total marrow irradiation for hematopoietic malignancies using volumetric modulated arc therapy: A review of treatment planning studies

Total Marrow Irradiation (TMI) has been introduced in the management of hematopoietic malignancies with the aim of reducing toxicities induced by total body irradiation. TMI is one of the most challenging planning and delivery techniques of radiotherapy, as the whole skeleton should be irradiated, while sparing nearby organs at risk (OARs). Target volumes of 7–10 k cm3 and healthy tissue volumes of 50–90 k cm3 should be considered and inverse treatment planning is needed. This review focused on aspects of TMI delivery using volumetric modulated arc therapy (VMAT). In particular, multiple arcs from isocenters with different positions are required for VMAT-TMI as the cranial-caudal lengths of patients are much larger than the jaw aperture. Therefore, many field junctions between arcs with different isocenters should be managed. This review covered, in particular, feasibility studies for managing multiple isocenters, optimization of plan parameters, plan optimization of the lower extremities, robustness of field junctions and dosimetric plan verification of VMAT-TMI. This review demonstrated the possibility of VMAT in delivering TMI with multi-arcs and multi-isocenters. Care should be paid in the patient repositioning, with particular attention to the cranial-caudal direction. Keywords: Volumetric modulated arc therapy (VMAT), Total Marrow Irradiation (TMI), Plan optimization, Radiotherap

advanced treatment planning strategies to enhance quality and efficiency of radiotherapy

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Recommendations on how to establish evidence from auto-segmentation software in radiotherapy

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Influence of organ motion on conformal vs. intensity-modulated pelvic radiotherapy for prostate cancer

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Implementation of a double scattering nozzle for Monte Carlo recalculation of proton plans with variable relative biological effectiveness

A constant relative biological effectiveness (RBE) of 1.1 is currently used in clinical proton therapy. However, the RBE varies with factors such as dose level, linear energy transfer (LET) and tissue type. Multiple RBE models have been developed to account for this biological variation. To enable recalculation of patients treated with double scattering (DS) proton therapy, including LET and variable RBE, we implemented and commissioned a Monte Carlo (MC) model of a DS treatment nozzle. The main components from the IBA nozzle were implemented in the FLUKA MC code. We calibrated and verified the following entities to experimental measurements: range of pristine Bragg peaks (PBPs) and spread-out Bragg peaks (SOBPs), energy spread, lateral profiles, compensator range degradation, and absolute dose. We recalculated two patients with different field setups, comparing FLUKA vs. treatment planning system (TPS) dose, also obtaining LET and variable RBE doses. We achieved good agreement between FLUKA and measurements. The range differences between FLUKA and measurements were for the PBPs within ±0.9 mm (83% ≤ 0.5 mm), and for SOBPs ±1.6 mm (82% ≤ 0.5 mm). The differences in modulation widths were below 5 mm (79% ≤ 2 mm). The differences in the distal dose fall off (D80%–D20%) were below 0.5 mm for all PBPs and the lateral penumbras diverged from measurements by less than 1 mm. The mean dose difference (RBE = 1.1) in the target between the TPS and FLUKA were below 0.4% in a three-field plan and below 1.4% in a four-field plan. A dose increase of 9.9% and 7.2% occurred when using variable RBE for the two patients, respectively. We presented a method to recalculate DS proton plans in the FLUKA MC code. The implementation was used to obtain LET and variable RBE dose and can be used for investigating variable RBE for previously treated patients.publishedVersio

A case-control study of linear energy transfer and relative biological effectiveness related to symptomatic brainstem toxicity following pediatric proton therapy

Background and purpose A fixed relative biological effectiveness (RBE) of 1.1 (RBE1.1) is used clinically in proton therapy even though the RBE varies with properties such as dose level and linear energy transfer (LET). We therefore investigated if symptomatic brainstem toxicity in pediatric brain tumor patients treated with proton therapy could be associated with a variable LET and RBE. Materials and methods 36 patients treated with passive scattering proton therapy were selected for a case-control study from a cohort of 954 pediatric brain tumor patients. Nine children with symptomatic brainstem toxicity were each matched to three controls based on age, diagnosis, adjuvant therapy, and brainstem RBE1.1 dose characteristics. Differences across cases and controls related to the dose-averaged LET (LETd) and variable RBE-weighted dose from two RBE models were analyzed in the high-dose region. Results LETd metrics were marginally higher for cases vs. controls for the majority of dose levels and brainstem substructures. Considering areas with doses above 54 Gy(RBE1.1), we found a moderate trend of 13% higher median LETd in the brainstem for cases compared to controls (P =.08), while the difference in the median variable RBE-weighted dose for the same structure was only 2% (P =.6). Conclusion Trends towards higher LETd for cases compared to controls were noticeable across structures and LETd metrics for this patient cohort. While case-control differences were minor, an association with the observed symptomatic brainstem toxicity cannot be ruled out.publishedVersio

Patterns of local recurrence and dose fractionation of adjuvant radiation therapy in 462 patients with soft tissue sarcoma of extremity and trunk wall

Purpose To study the impact of dose fractionation of adjuvant radiation therapy (RT) on local recurrence (LR) and the relation of LR to radiation fields. Methods and Materials LR rates were analyzed in 462 adult patients with soft tissue sarcoma who underwent surgical excision and adjuvant RT at five Scandinavian sarcoma centers from 1998 to 2009. Medical records were reviewed for dose fractionation parameters and to determine the location of the LR relative to the radiation portals. Results Fifty-five of 462 patients developed a LR (11.9%). Negative prognostic factors included intralesional surgical margin (hazard ratio [HR]: 7.83, 95% confidence interval [CI]: 3.08-20.0), high malignancy grade (HR: 5.82, 95% CI: 1.31-25.8), age at diagnosis (HR per 10 years: 1.27, 95% CI: 1.03-1.56), and malignant peripheral nerve sheath tumor histological subtype (HR: 6.66, 95% CI: 2.56-17.3). RT dose was tailored to margin status. No correlation between RT dose and LR rate was found in multiple Cox regression analysis. The majority (65%) of LRs occurred within the primary RT volume. Conclusions No significant dose–response effect of adjuvant RT was demonstrated. Interestingly, patients given 45-Gy accelerated RT (1.8 Gy twice daily/2.5 weeks) had the best local outcome. A total dose of 50 Gy in 25 fractions seemed adequate following wide margin surgery. The risk of LR was associated with histopathologic subtype, which should be included in the treatment algorithm of adjuvant RT in soft tissue sarcoma.publishedVersio