Temperature-controlled power modulation compensates for heterogeneous nanoparticle distributions: a computational optimization analysis for magnetic hyperthermia

Purpose: To study, with computational models, the utility of power modulation to reduce tissue temperature heterogeneity for variable nanoparticle distributions in magnetic nanoparticle hyperthermia.

Methods: Tumour and surrounding tissue were modeled by elliptical two- and three-dimensional computational phantoms having six different nanoparticle distributions. Nanoparticles were modeled as point heat sources having amplitude-dependent loss power. The total number of nanoparticles was fixed, and their spatial distribution and heat output were varied. Heat transfer was computed by solving the Pennes’ bioheat equation using finite element methods (FEM) with temperature-dependent blood perfusion. Local temperature was regulated using a proportional-integral-derivative (PID) controller. Tissue temperature, thermal dose and tissue damage were calculated. The required minimum thermal dose delivered to the tumor was kept constant, and heating power was adjusted for comparison of both the heating methods.

Results: Modulated power heating produced lower and more homogeneous temperature distributions than did constant power heating for all studied nanoparticle distributions. For a concentrated nanoparticle distribution, located off-center within the tumor, the maximum temperatures inside the tumor were 16% lower for modulated power heating when compared to constant power heating. This resulted in less damage to surrounding normal tissue. Modulated power heating reached target thermal doses up to nine-fold more rapidly when compared to constant power heating.

Conclusions: Controlling the temperature at the tumor-healthy tissue boundary by modulating the heating power of magnetic nanoparticles demonstrably compensates for a variable nanoparticle distribution to deliver effective treatment.     

Survival and Outcomes of Newly Diagnosed Multiple Myeloma Patients Stratified by Transplant Status 2007-2018: Retrospective Analysis from the Canadian Myeloma Research Group Database

BackgroundConsiderable progress has been made in therapeutic options for multiple myeloma (MM). Understanding the current landscape of MM treatment options and associated outcomes in the real world is important in providing key insights into clinical and knowledge gaps which could be targeted for further optimization.MethodsThe Canadian Myeloma Research Group Database (CMRG-DB) is a prospectively maintained disease-specific database with >7000 patients. The objective of this study was to describe the trends in the treatment landscape and outcomes including early mortality, time to next treatment, and overall survival (OS) in each line of treatment stratified by autologous stem cell transplant (ASCT) receipt among newly-diagnosed MM patients in Canada between 2007 and 2018.ResultsA total of 5154 patients were identified among which 3030 patients (58.8%) received an upfront ASCT and 2124 (41.2%) did not. At diagnosis, the median age was 64 years and 58.6% were males. Bortezomib and lenalidomide were most frequently used (>50%) in first and second-line treatment respectively among both the ASCT and non-ASCT cohort. The median OS was 122.0 months (95% Cl 115.0-135.0 months) and 54.3 months (95% CI 50.8-58.8 months) for the ASCT and non-ASCT cohort respectively with an incremental decrease in OS in each subsequent line of treatment.ConclusionWe present the largest study to date in the Canadian landscape showing the characteristics, therapy usage, and outcomes among MM patients. This information will be critical in benchmarking current outcomes and provide key insight into areas of unmet needs and gaps for improvement of MM patients nationally.     

Computational dose visualization & comparison in total skin electron treatment suggests superior coverage by the rotational versus the Stanford technique

Introduction/BackgroundThe goal of Total Skin Electron Therapy (TSET) is to achieve a uniform surface dose, although assessment of this is never really done and typically limited points are sampled. A computational treatment simulation approach was developed to estimate dose distributions over the body surface, to compare uniformity of (i) the 6 pose Stanford technique and (ii) the rotational technique.MethodsThe relative angular dose distributions from electron beam irradiation was calculated by Monte Carlo simulation for cylinders with a range of diameters, approximating body part curvatures. These were used to project dose onto a 3D body model of the TSET patient's skin surfaces. Computer animation methods were used to accumulate the dose values, for display and analysis of the homogeneity of coverage.ResultsThe rotational technique provided more uniform coverage than the Stanford technique. Anomalies of under dose were observed in lateral abdominal regions, above the shoulders and in the perineum. The Stanford technique had larger areas of low dose laterally. In the rotational technique, 90% of the patient's skin was within ±10% of the prescribed dose, while this percentage decreased to 60% or 85% for the Stanford technique, varying with patient body mass. Interestingly, the highest discrepancy was most apparent in high body mass patients, which can be attributed to the loss of tangent dose at low angles of curvature.Discussion/ConclusionThis simulation and visualization approach is a practical means to analyze TSET dose, requiring only optical surface body topography scans. Under- and over-exposed body regions can be found, and irradiation could be customized to each patient. Dose Area Histogram (DAH) distribution analysis showed the rotational technique to have better uniformity, with most areas within 10% of the umbilicus value. Future use of this approach to analyze dose coverage is possible as a routine planning tool.     

T1~T2期乳腺癌保乳术后化疗后程同步大分割放疗前瞻性Ⅰ期临床研究

目的 前瞻性评估T1~T2期乳腺癌保乳术后化疗后程大分割放疗的不良反应和耐受性，以及在缩短治疗时间、减轻患者经济负担等方面的价值。方法 共入组20例T1~T2期乳腺癌保乳术后患者，所有患者于末次多西他赛化疗前开始大分割放疗。观察急性放射反应、治疗完成率及无病生存率、住院时间及住院费用等。结果 治疗完成率100%。主要不良反应为血液学毒性（白细胞减少）及皮肤反应，患者均可耐受。中位随访时间为30.1个月，随访率100%。美容效果良好率100%。平均总治疗时间为4周，总住院治疗费用节省约1万元。21个月无病生存率为100%。结论 T1~T2期乳腺癌保乳术后可耐受同步大分割放化疗，局部控制好，美容效果佳，且具有较高的卫生经济学价值。     

An Evidence-Based Review of Total Body Irradiation

The purpose of this literature review is to investigate clinical treatment methods of total body irradiation within the context of a clinical department adopting a paediatric cohort with no existing technique. An extensive review of the literature was conducted using PubMed, Science Direct, Google Scholar, and Clinicians Knowledge Network. Articles were limited to nonhelical tomotherapy, nonparticle therapies, and those using hyperfractionated regimes. Total marrow irradiation was excluded because of national treatment and trial limitations. Of the numerous patient positioning methods present within the literature, the most comfortable and reproducible positioning methods for total body irradiation include both supine and the supine and/or prone combination. These positions increased stability and patient comfort during treatment, while also facilitating computed tomography data acquisition at the simulation stage. Ideally, dose calculations should be performed using a three-dimensional treatment planning system and quality assurance procedures that include in vivo dosimetry measurements. The available literature also suggests inhomogeneity correction factors and intensity modulation are superior to conventional open field techniques and should be implemented within developing protocols. Dynamic machine dose modulation is suggested to reduce department impact, removing the need for tissue compensators and accessory shielding devices, while providing significant improvements to treatment time and dose accuracy. Further long-term survival and intensity modulation studies are warranted, including direct comparisons of both dose modulation and treatment efficiency.     

Stereotactic Body Radiotherapy Versus Metastasectomy in Patients With Pulmonary Metastases From Soft Tissue Sarcoma

The lung is the preferred site of metastasis from soft tissue sarcoma (STS). This systematic review aims to evaluate the outcomes of stereotactic body radiotherapy (SBRT) and metastasectomy (MTS) for the treatment of lung metastases from STS. A systematic review was carried out according to the PRISMA protocol. PubMed, Medline, EMBASE, Cochrane Library, Ovid and Web of Knowledge databases were searched for English-language articles to December 2018 using a predefined strategy. Retrieved studies were independently screened and rated for relevance. Data were extracted by two researchers. In total, there were 1306 patients with STS: 1104 underwent MTS and 202 had SBRT. The mean age ranged from 40 to 55.8 years in the MTS group and from 47.9 to 64 years in the SBRT group. The cumulative death rate was 72% (95% confidence interval 59–85%) in the MTS group and 56% (38–74%) in the SBRT group. The cumulative mean overall survival time was 46.7 months (36.4–57.0%) in the MTS group and 47.6 months (33.7–61.5%) in the SBRT group. The cumulative rate of patients alive with disease was 5% (2–9%) in the MTS group and 15% (6–36%) in the SBRT group. Finally, the cumulative rate of patients alive without disease in the two groups was 19% (9–29%) and 20% (10–50%), respectively. Our study showed that local treatment of pulmonary metastases from STS with SBRT, compared with surgery, was associated with a lower cumulative overall death rate and similar overall survival time and survival rates without disease. By contrast, SBRT was associated with a higher survival rate with disease than MTS. Large randomised trials are necessary to confirm these findings and to establish whether SBRT may be a reliable option for early stage disease.