Characterisation and Quenching Correction for an Al2O3:C Optical Fibre Real Time System in Therapeutic Proton, Helium, and Carbon-Charged Beams.

Real time radioluminescence fibre-based detectors were investigated for application in proton, helium, and carbon therapy dosimetry. The Al2O3:C probes are made of one single crystal (1 mm) and two droplets of micro powder in two sizes (38 µm and 4 µm) mixed with a water-equivalent binder. The fibres were irradiated behind different thicknesses of solid slabs, and the Bragg curves presented a quenching effect attributed to the nonlinear response of the radioluminescence (RL) signal as a function of linear energy transfer (LET). Experimental data and Monte Carlo simulations were utilised to acquire a quenching correction method, adapted from Birks' formulation, to restore the linear dose-response for particle therapy beams. The method for quenching correction was applied and yielded the best results for the '4 µm' optical fibre probe, with an agreement at the Bragg peak of 1.4% (160 MeV), and 1.5% (230 MeV) for proton-charged particles; 2.4% (150 MeV/u) for helium-charged particles and of 4.8% (290 MeV/u) and 2.9% (400 MeV/u) for the carbon-charged particles. The most substantial deviations for the '4 µm' optical fibre probe were found at the falloff regions, with ~3% (protons), ~5% (helium) and 6% (carbon).

Characterisation and classification of oligometastatic disease: a European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer consensus recommendation.

Oligometastatic disease has been proposed as an intermediate state between localised and systemically metastasised disease. In the absence of randomised phase 3 trials, early clinical studies show improved survival when radical local therapy is added to standard systemic therapy for oligometastatic disease. However, since no biomarker for the identification of patients with true oligometastatic disease is clinically available, the diagnosis of oligometastatic disease is based solely on imaging findings. A small number of metastases on imaging could represent different clinical scenarios, which are associated with different prognoses and might require different treatment strategies. 20 international experts including 19 members of the European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer OligoCare project developed a comprehensive system for characterisation and classification of oligometastatic disease. We first did a systematic review of the literature to identify inclusion and exclusion criteria of prospective interventional oligometastatic disease clinical trials. Next, we used a Delphi consensus process to select a total of 17 oligometastatic disease characterisation factors that should be assessed in all patients treated with radical local therapy for oligometastatic disease, both within and outside of clinical trials. Using a second round of the Delphi method, we established a decision tree for oligometastatic disease classification together with a nomenclature. We agreed oligometastatic disease as the overall umbrella term. A history of polymetastatic disease before diagnosis of oligometastatic disease was used as the criterion to differentiate between induced oligometastatic disease (previous history of polymetastatic disease) and genuine oligometastatic disease (no history of polymetastatic disease). We further subclassified genuine oligometastatic disease into repeat oligometastatic disease (previous history of oligometastatic disease) and de-novo oligometastatic disease (first time diagnosis of oligometastatic disease). In de-novo oligometastatic disease, we differentiated between synchronous and metachronous oligometastatic disease. We did a final subclassification into oligorecurrence, oligoprogression, and oligopersistence, considering whether oligometastatic disease is diagnosed during a treatment-free interval or during active systemic therapy and whether or not an oligometastatic lesion is progressing on current imaging. This oligometastatic disease classification and nomenclature needs to be prospectively evaluated by the OligoCare study.

Oncological outcome, postoperative complications, and mammographic changes after intraoperative radiotherapy with electrons (IOERT) as a boost in a large single-institution cohort of breast cancer patients.

Advantages of using intraoperative radiotherapy with electrons (IOERT) as a boosting modality in breast-conserving therapy include the direct visualization of the tumor bed, a reduced skin dose, and patient convenience. We report oncological outcome, postoperative complication rate, and mammographic changes on follow-up imaging in women treated at our institution with IOERT as a boost modality in breast-conserving therapy for early-stage breast carcinoma. Between January 2007 and June 2018, 763 consecutive patients were enrolled. During breast-conserving surgery, an IOERT boost of 9 Gy was applied, followed by whole breast irradiation (WBI). At a median follow-up of 62.2 months (range: 0.5-135), 13 in-breast recurrences were observed, yielding a local tumor control rate of 98.4% at 5 years. In multivariable analysis, high tumor grading was predictive for local recurrence (HR = 5.6; 95%CI: 1.19-26.2). A total of 27 (3.5%) patients developed any kind of postoperative complication. None of the tumor characteristics nor any of the IOERT technical parameters were predictive for development of a postoperative complication. On follow-up imaging, 145 patients with mammographic changes BIRADS score ≥3 were found of which 50.3% required a biopsy. Only 17 patients had positive biopsies; none of the IOERT parameters were predictive for false-positive imaging. A 9 Gy IOERT boost combined with postoperative WBI provided outstanding local control rates, was well-tolerated, with limited postoperative complications. However, radiologists must be aware of a presumable higher prevalence of mammographic changes after IORT as a boost.

A phase III randomized-controlled, single-blind trial to improve quality of life with stereotactic body radiotherapy for patients with painful bone metastases (ROBOMET).

BACKGROUND: Bone metastases represent an important source of morbidity in cancer patients, mostly due to severe pain. Radiotherapy is an established symptomatic treatment for painful bone metastases, however, when conventional techniques are used, the effectiveness is moderate. Stereotactic body radiotherapy (SBRT), delivering very high doses in a limited number of fractions in a highly conformal manner, could potentially be more effective and less toxic. METHODS: This is a phase III, randomized-controlled, single-blind, multicenter study evaluating the response rate of antalgic radiotherapy for painful bone metastases and the acute toxicity associated with this treatment. A total of 126 patients will be randomly assigned to receive either the standard schedule of a single fraction of 8.0 Gy delivered through three-dimensional conformal radiotherapy or a single fraction of 20.0 Gy delivered through SBRT. Primary endpoint is pain response at the treated site at 1 month after radiotherapy. Secondary endpoints are pain flare at 24-48-72 h after radiotherapy, duration of pain response, re-irradiation need, acute toxicity, late toxicity, quality of life and subsequent serious skeletal events. In a supplementary analysis, patient-compliance for a paper-and-pencil questionnaire will be compared with an electronic mode. DISCUSSION: If a dose-escalated approach within the context of single fraction stereotactic body radiotherapy could improve the pain response to radiotherapy and minimize acute toxicity, this would have an immediate impact on the quality of life for a large number of patients with advanced cancer. Potential disadvantages of this technique include increased pain flare or a higher incidence of radiation-induced fractures. TRIAL REGISTRATION: The Ethics committee of the GZA Hospitals (B099201732915) approved this study on September 4th 2018. Trial registered on Clinicaltrials.gov ( NCT03831243 ) on February 5th 2019.

Feasibility of using the Vero SBRT system for intracranial SRS.

The Vero SBRT system was benchmarked in a planning study against the Novalis SRS system for quality of delivered dose distributions to intracranial lesions and assessing the Vero system's capacity for SRS. A total of 27 patients with one brain lesion treated on the Novalis system, with 3 mm leaf width MLC and C-arm gantry, were replanned for Vero, with a 5 mm leaf width MLC mounted on an O-ring gantry allowing rotations around both the horizontal and vertical axis. The Novalis dynamic conformal arc (DCA) planning included vertex arcs, using 90° couch rotation. These vertex arcs cannot be reproduced with Vero due to the mechanical limitations of the O-ring gantry. Alternative class solutions were investigated for the Vero. Additionally, to distinguish between the effect of MLC leaf width and different beam arrangements on dose distributions, the Vero class solutions were also applied for Novalis. In addition, the added value of noncoplanar IMRT was investigated in this study. Quality of the achieved dose distributions was expressed in the conformity index (CI) and gradient index (GI), and compared using a paired Student's t-test with statistical significance for p-values ≤ 0.05. For lesions larger than 5 cm3, no statistical significant difference in conformity was observed between Vero and Novalis, but for smaller lesions, the dose distributions showed a significantly better conformity for the Novalis (ΔCI = 13.74%, p = 0.0002) mainly due to the smaller MLC leaf width. Using IMRT on Vero reduces this conformity difference to nonsignificant levels. The cutoff for achieving a GI around 3, characterizing a sharp dose falloff outside the target volume was 4 cm3 for Novalis and 7 cm3 for Vero using DCA technique. Using noncoplanar IMRT, this threshold was reduced to 3 cm3 for the Vero system. The smaller MLC and the presence of the vertex fields allow the Novalis system to better conform the dose around the lesion and to obtain steeper dose falloff outside the lesion. Comparable dosimetric characteristics can be achieved with Vero for lesions larger than 3 cm3 and using IMRT.

Multi-institutional generalizability of a plan complexity machine learning model for predicting pre-treatment quality assurance results in radiotherapy.

Background and purpose: Treatment plans in radiotherapy are subject to measurement-based pre-treatment verifications. In this study, plan complexity metrics (PCMs) were calculated per beam and used as input features to develop a predictive model. The aim of this study was to determine the robustness against differences in machine type and institutional-specific quality assurance (QA). Material and methods: A number of 567 beams were collected, where 477 passed and 90 failed the pre-treatment QA. Treatment plans of different anatomical regions were included. One type of linear accelerator was represented. For all beams, 16 PCMs were calculated. A random forest classifier was trained to distinct between acceptable and non-acceptable beams. The model was validated on other datasets to investigate its robustness. Firstly, plans for another machine type from the same institution were evaluated. Secondly, an inter-institutional validation was conducted on three datasets from different centres with their associated QA. Results: Intra-institutionally, the PCMs beam modulation, mean MLC gap, Q1 gap, and Modulation Complexity Score were the most informative to detect failing beams. Eighty-tree percent of the failed beams (15/18) were detected correctly. The model could not detect over-modulated beams of another machine type. Inter-institutionally, the model performance reached higher accuracy for centres with comparable equipment both for treatment and QA as the local institute. Conclusions: The study demonstrates that the robustness decreases when major differences appear in the QA platform or in planning strategies, but that it is feasible to extrapolate institutional-specific trained models between centres with similar clinical practice. Predictive models should be developed for each machine type.

Automated determination of the ion-recombination correction factor (ksat) in ultra-high dose rate electron radiation therapy.

BACKGROUND: Plane-parallel ionization chambers are the recommended secondary standard systems for clinical reference dosimetry of electrons. Dosimetry in high dose rate and dose-per-pulse (DPP) is challenging as ionization chambers are subject to ion recombination, especially when dose rate and/or DPP is increased beyond the range of conventional radiotherapy. The lack of universally accepted models for correction of ion recombination in UDHR is still an issue as it is, especially in FLASH-RT research, which is crucial in order to be able to accurately measure the dose for a wide range of dose rates and DPPs. PURPOSE: The objective of this study was to show the feasibility of developing an Artificial Intelligence model to predict the ion-recombination factor-ksat for a plane-parallel Advanced Markus ionization chamber for conventional and ultra-high dose rate electron beams based on machine parameters. In addition, the predicted ksat of the AI model was compared with the current applied analytical models for this correction factor. METHODS: A total number of 425 measurements was collected with a balanced variety in machine parameter settings. The specific ksat values were determined by dividing the output of the reference dosimeter (optically stimulated luminescence [OSL]) by the output of the AM chamber. Subsequently, a XGBoost regression model was trained, which used the different machine parameters as input features and the corresponding ksat value as output. The prediction accuracy of this regression model was characterized by R2-coefficient of determination, mean absolute error and root mean squared error. In addition, the model was compared with the Two-Voltage (TVA) method and empirical Petersson model for 19 different dose-per-pulse values ranging from conventional to UDHR regimes. The Akiake Information criterion (AIC) was calculated for the three different models. RESULTS: The XGBoost regression model reached a R2-score of 0.94 on the independent test set with a MAE of 0.067 and RMSE of 0.106. For the additional 19 random data points, the ksat values predicted by the XGBoost model showed to be in agreement, within the uncertainties, with the ones determined by the Petersson model and better than the TVA method for doses per pulse >3.5 Gy with a maximum deviation from the ground truth of 14.2%, 16.7%, and -36.0%, respectively, for DPP >4 Gy. CONCLUSION: The proposed method of using AI for ksat determination displays efficiency. For the investigated DPPs, the ksat values obtained with the XGBoost model were in concurrence with the ones obtained with the current available analytical models within the boundaries of uncertainty, certainly for the DPP characterizing UDHR. But the overall performance of the AI model, taking the number of free parameters into account, lacked efficiency. Future research should optimize the determination of the experimental ksat, and investigate the determination the ksat for DPPs higher than the ones investigated in this study, while also evaluating the prediction of the proposed XGBoost model for UDHR machines of different centers.

Long-Term Results of a Phase 1 Dose Escalation Trial of Ablative Stereotactic Body Radiation Therapy.

PURPOSE: Stereotactic body radiation therapy is increasingly used for oligometastatic disease as well as palliation, but treatment protocols for nonspine bone and nodal metastases are lacking, with a wide variety of schedules applied. METHODS AND MATERIALS: A prospective dose-escalation trial was initiated, involving 90 patients, among whom 52 (58%) had primary prostate tumors, 13 had breast tumors (14%), and 25 (28%) had other primary tumor types. All visible lymph node or nonspine bone oligometastases were treated in 3 consecutive cohorts: 5 × 7.0 Gy, 3 × 10.0 Gy, or 1 × 20.0 Gy. RESULTS: Initial results revealed no dose-limiting toxicity after a median follow-up of 17.2 months. This update provides information on long-term toxicity, local failure (LF), and progression-free survival (PFS). After a median follow-up of 50 months, no new safety signals were observed. Grade 2 toxicity was 13%, 7% and 10% in the respective cohorts (P = .9), without grade 3 to 5 toxicities. LF rates were 9%, 3%, and 6% (P = .5) for the respective treatment groups, with an overall cumulative risk of LF of 7% (95% CI, 2-12) at 4 years. Median PFS was 16.5 months (95% CI, 9.8-21.5), and 4-year PFS was 21% (95% CI, 14-32). Median overall survival across groups was not reached (95% CI, 52.8 - not reached), 4-year OS was 68% (95% CI, 59-78). A subset of patients (23%) remained long-term disease-free, 37% had oligoprogressive disease at first recurrence and 40% developed polymetastatic relapse. CONCLUSIONS: The safe and effective use of dose-escalated single-fraction stereotactic body radiation therapy for bone and lymph node metastases is supported by this trial, especially considering patient-convenience and cost-effectiveness. Caution is needed when generalizing these outcomes beyond breast and prostate cancer, given their underrepresentation in our study.

The potential of helical tomotherapy in the treatment of head and neck cancer.

A decade after its first introduction into the clinic, little is known about the clinical impact of helical tomotherapy (HT) on head and neck cancer (HNC) treatment. Therefore, we analyzed the basics of this technique and reviewed the literature regarding HT's potential benefit in HNC. The past two decades have been characterized by a huge technological evolution in photon beam radiotherapy (RT). In HNC, static beam intensity-modulated radiotherapy (IMRT) has shown superiority over three-dimensional conformal RT in terms of xerostomia and is considered the standard of care. However, the next-generation IMRT, the rotational IMRT, has been introduced into the clinic without any evidence of superiority over static beam IMRT other than being substantially faster. Of these rotational techniques, HT is the first system especially developed for IMRT in combination with image-guided RT. HT is particularly promising for the treatment of HNC because its sharp dose gradients maximally spare the many radiosensitive organs at risk nearby. In addition, HT's integrated computed tomography scan assures a very precise dose administration and allows for some adaptive RT. Because HT is specifically developed for IMRT in combination with (integrated) image-guidance, it allows for precise dose distribution ("dose painting"), patient setup, and dose delivery. As such, it is an excellent tool for difficult HNC irradiation. The literature on the clinical results of HT in HNC all show excellent short-term (≤2 years) results with acceptable toxicity profiles. However, properly designed trials are still warranted to further substantiate these results.

Parameterisation of Respiratory Impedance in Lung Cancer Patients From Forced Oscillation Lung Function Test.

OBJECTIVE: This study aims to analyze the contribution and application of forced oscillation technique (FOT) devices in lung cancer assessment. Two devices and corresponding methods can be feasible to distinguish among various degrees of lung tissue heterogeneity. METHODS: The outcome respiratory impedance Zrs (in terms of resistance Rrs and reactance Xrs) is calculated for FOT and is interpreted in physiological terms by being fitted with a fractional-order impedance mathematical model (FOIM). The non-parametric data obtained from the measured signals of pressure and flow is correlated with an analogous electrical model to the respiratory system resistance, compliance, and elastance. The mechanical properties of the lung can be captured through Gr to define the damping properties and Hr to describe the elastance of the lung tissue, their ratio representing tissue heterogeneity ηr. RESULTS: We validated our hypotheses and methods in 17 lung cancer patients where we showed that FOT is suitable for non-invasively measuring their respiratory impedance. FOIM models are efficient in capturing frequency-dependent impedance value variations. Increased heterogeneity and structural changes in the lungs have been observed. The results present inter- and intra-patient variability for the performed measurements. CONCLUSION: The proposed methods and assessment of the respiratory impedance with FOT have been demonstrated useful for characterizing mechanical properties in lung cancer patients. SIGNIFICANCE: This correlation analysis between the measured clinical data motivates the use of the FOT devices in lung cancer patients for diagnosis of lung properties and follow-up of the respiratory function modified due to the applied radiotherapy treatment.

Assessing the impact of adaptations to the clinical workflow in radiotherapy using transit in vivo dosimetry.

Background and Purpose: Currently in-vivo dosimetry (IVD) is primarily used to identify individual patient errors in radiotherapy. This study investigated possible correlations of observed trends in transit IVD results, with adaptations to the clinical workflow, aiming to demonstrate the possibility of using the bulk data for continuous quality improvement. Materials and methods: In total 84,100 transit IVD measurements were analyzed of all patients treated between 2018 and 2022, divided into four yearly periods. Failed measurements (FM) were divided per pathology and into four categories of causes of failure: technical, planning and positioning problems, and anatomic changes. Results: The number of FM due to patient related problems gradually decreased from 9.5% to 6.6%, 6.1% and 5.6% over the study period. FM attributed to positioning problems decreased from 10.0% to 4.9% in boost breast cancer patients after introduction of extra imaging, from 9.1% to 3.9% in Head&Neck patients following education of radiation therapists on positioning of patients' shoulders, from 6.1% to 2.8% in breast cancer patients after introduction of ultrahypofractionated breast radiotherapy with daily online pre-treatment imaging and from 11.2% to 4.3% in extremities following introduction of immobilization with calculated couch parameters and a Surface Guided Radiation Therapy solution. FM related to anatomic changes decreased from 10.2% to 4.0% in rectum patients and from 6.7% to 3.3% in prostate patients following more patient education from dieticians. Conclusions: Our study suggests that IVD can be a powerful tool to assess the impact of adaptations to the clinical workflow and its use for continuous quality improvement.

The use of in-vivo dosimetry to identify head and neck cancer patients needing adaptive radiotherapy.

BACKGROUND AND PURPOSE: Head and neck cancer (HNC) patients experiencing anatomical changes during their radiotherapy (RT) course may benefit from adaptive RT (ART). We investigated the sensitivity of an electronic portal imaging device (EPID)-based in-vivo dosimetry (EIVD) system to detect patients that require ART and identified its limitations. MATERIALS AND METHODS: A retrospective study was conducted for 182 HNC patients: laryngeal cancer without elective lymph nodes (group A), postoperative RT (group B) and primary RT including elective lymph nodes (group C). The effect of anatomical changes on the dose distribution and volumetric changes was quantified. The receiver operating characteristic curve was used to obtain the optimal cut-off value for the gamma passing rate (%GP) with a dose difference of 3% and a distance to agreement of 3 mm. RESULTS: Fifty HNC patients receiving ART were analyzed: 1 in group A, 10 in group B and 39 in group C. Failed fractions (FFs) occurred in 1/1, 6/10 and 23/39 cases before ART in group A, B and C respectively. In the four cases in group B without FFs, only minor dosimetric changes were observed. One of the cases in group C without FFs had significant dosimetric changes (false negative). Three cases received ART because of clinical reasons that cannot be detected by EIVD. The optimal cut-off value for the %GP was 95%/95.2% for old/new generation machines respectively. CONCLUSION: EIVD combined with 3D imaging techniques can be synergistic in the detection of anatomical changes in HNC patients who benefit from ART.

A geometry and dose-volume based performance monitoring of artificial intelligence models in radiotherapy treatment planning for prostate cancer.

Background and Purpose: Clinical Artificial Intelligence (AI) implementations lack ground-truth when applied on real-world data. This study investigated how combined geometrical and dose-volume metrics can be used as performance monitoring tools to detect clinically relevant candidates for model retraining. Materials and Methods: Fifty patients were analyzed for both AI-segmentation and planning. For AI-segmentation, geometrical (Standard Surface Dice 3 mm and Local Surface Dice 3 mm) and dose-volume based parameters were calculated for two organs (bladder and anorectum) to compare AI output against the clinically corrected structure. A Local Surface Dice was introduced to detect geometrical changes in the vicinity of the target volumes, while an Absolute Dose Difference (ADD) evaluation increased focus on dose-volume related changes. AI-planning performance was evaluated using clinical goal analysis in combination with volume and target overlap metrics. Results: The Local Surface Dice reported equal or lower values compared to the Standard Surface Dice (anorectum: (0.93 ± 0.11) vs (0.98 ± 0.04); bladder: (0.97 ± 0.06) vs (0.98 ± 0.04)). The ADD metric showed a difference of (0.9 ± 0.8)Gy for the anorectum D1cm3. The bladder D5cm3 reported a difference of (0.7 ± 1.5)Gy. Mandatory clinical goals were fulfilled in 90 % of the DLP plans. Conclusions: Combining dose-volume and geometrical metrics allowed detection of clinically relevant changes, applied to both auto-segmentation and auto-planning output and the Local Surface Dice was more sensitive to local changes compared to the Standard Surface Dice. This monitoring is able to evaluate AI behavior in clinical practice and allows candidate selection for active learning.

Optically stimulated luminescence system as an alternative for radiochromic film for 2D reference dosimetry in UHDR electron beams.

Radiotherapy is part of the treatment of over 50% of cancer patients. Its efficacy is limited by the radiotoxicity to the healthy tissue. FLASH-RT is based on the biological effect that ultra-high dose rates (UHDR) and very short treatment times strongly reduce normal tissue toxicity, while preserving the anti-tumoral effect. Despite many positive preclinical results, the translation of FLASH-RT to the clinic is hampered by the lack of accurate dosimetry for UHDR beams. To date radiochromic film is commonly used for dose assessment but has the drawback of lengthy and cumbersome read out procedures. In this work, we investigate the equivalence of a 2D OSL system to radiochromic film dosimetry in terms of dose rate independency. The comparison of both systems was done using the ElectronFlash linac. We investigated the dose rate dependence by variation of the (1) modality, (2) pulse repetition frequency, (3) pulse length and (4) source to surface distance. Additionally, we compared the 2D characteristics by field size measurements. The OSL calibration showed transferable between conventional and UHDR modality. Both systems are equally independent of average dose rate, pulse length and instantaneous dose rate. The OSL system showed equivalent in field size determination within 3 sigma. We show the promising nature of the 2D OSL system to serve as alternative for radiochromic film in UHDR electron beams. However, more in depth characterization is needed to assess its full potential.

Small airways function in breast cancer patients before and after radiotherapy.

Radiotherapy treatments for early stage breast cancer patients potentially affect the lung in its most distal air spaces, and previous studies have indicated consistently low baseline values for diffusing capacity in breast cancer patients. We aimed to quantitatively assess baseline small airway function and the acute effects of radiotherapy in breast cancer patients with no confounding effects from respiratory disease or considerable smoking history. In 60 breast cancer patients selected from an ongoing randomized controlled trial, the small airways function was assessed at baseline and 3 months later, after having received either conventional radiotherapy (CR; n = 26) or hypofractionated tomotherapy (TT; n = 34). All indices of small airway function in breast cancer patients were found to be indistinguishable from healthy controls. The total lung capacity was significantly decreased and ventilation heterogeneity was significantly increased 3 months after baseline in the CR arm, but not in the TT arm. When corrected for hemoglobin and lung volume, pulmonary diffusing capacity was not affected by radiotherapy in either treatment arm. Alternatively, discarding patients receiving chemotherapy or loco-regional treatment did not affect these results. We conclude that middle-aged women with breast cancer, but no history of respiratory disease, have normal baseline small airways function. Conventional radiotherapy induces a restrictive pattern and increases heterogeneity of ventilation, the latter most likely resulting from differential expansion between locally irradiated peripheral lung zones and the remainder of the lung. The TT modality did not lead to any such changes.

Quantification of cerebral tumour blood flow and permeability with T1-weighted dynamic contrast enhanced MRI: a feasibility study.

OBJECTIVES: Recently, T1-weighted DCE-MRI was proposed as an alternative to T2*-weighted DSC-MRI for the quantification of perfusion and permeability in brain tumors. The aim of the present feasibility study was to explore the clinical potential of the technique in different tumor types using a case-based review of initial results. PATIENTS AND METHODS: The method for data analysis was adapted from cerebral perfusion CT and applied in this study to a small group of patients with grade IV glioma and other brain tumors. The possible use of the proposed methodology was also explored for characterizing, following-up and planning the therapy of brain tumors. RESULTS: Parametric maps clearly differentiated tumor from the surrounding brain tissue, and also distinguished areas within the tumor presenting with different characteristics, thereby allowing identification of significant target areas for biopsy and/or treatment. Differences in cerebral blood flow (CBF) and lower extraction fractions (E) were observed in various tumors. Progression from a grade II to grade IV glioma over the course of a year was characterized by an increase in CBF and a decrease in E. CONCLUSION: DCE-MRI-based quantitative perfusion and permeability may be helpful for tumor-grade characterization, biopsy guidance, radiotherapy planning, radiotherapy monitoring and clinical follow-up, thereby improving the non-invasive characterization of brain tumors.

Delivering affordable cancer care in high-income countries.

The burden of cancer is growing, and the disease is becoming a major economic expenditure for all developed countries. In 2008, the worldwide cost of cancer due to premature death and disability (not including direct medical costs) was estimated to be US$895 billion. This is not simply due to an increase in absolute numbers, but also the rate of increase of expenditure on cancer. What are the drivers and solutions to the so-called cancer-cost curve in developed countries? How are we going to afford to deliver high quality and equitable care? Here, expert opinion from health-care professionals, policy makers, and cancer survivors has been gathered to address the barriers and solutions to delivering affordable cancer care. Although many of the drivers and themes are specific to a particular field-eg, the huge development costs for cancer medicines-there is strong concordance running through each contribution. Several drivers of cost, such as over-use, rapid expansion, and shortening life cycles of cancer technologies (such as medicines and imaging modalities), and the lack of suitable clinical research and integrated health economic studies, have converged with more defensive medical practice, a less informed regulatory system, a lack of evidence-based sociopolitical debate, and a declining degree of fairness for all patients with cancer. Urgent solutions range from re-engineering of the macroeconomic basis of cancer costs (eg, value-based approaches to bend the cost curve and allow cost-saving technologies), greater education of policy makers, and an informed and transparent regulatory system. A radical shift in cancer policy is also required. Political toleration of unfairness in access to affordable cancer treatment is unacceptable. The cancer profession and industry should take responsibility and not accept a substandard evidence base and an ethos of very small benefit at whatever cost; rather, we need delivery of fair prices and real value from new technologies.

Model Calibration of Pharmacokinetic-Pharmacodynamic Lung Tumour Dynamics for Anticancer Therapies.

Individual curves for tumor growth can be expressed as mathematical models. Herein we exploited a pharmacokinetic-pharmacodynamic (PKPD) model to accurately predict the lung growth curves when using data from a clinical study. Our analysis included 19 patients with non-small cell lung cancer treated with specific hypofractionated regimens, defined as stereotactic body radiation therapy (SBRT). The results exhibited the utility of the PKPD model for testing growth hypotheses of the lung tumor against clinical data. The model fitted the observed progression behavior of the lung tumors expressed by measuring the tumor volume of the patients before and after treatment from CT screening. The changes in dynamics were best captured by the parameter identified as the patients' response to treatment. Median follow-up times for the tumor volume after SBRT were 126 days. These results have proven the use of mathematical modeling in preclinical anticancer investigations as a potential prognostic tool.

Machine learning-based treatment couch parameter prediction in support of surface guided radiation therapy.

Purpose: A fully independent, machine learning-based automatic treatment couch parameters prediction was developed to support surface guided radiation therapy (SGRT)-based patient positioning protocols. Additionally, this approach also acts as a quality assurance tool for patient positioning. Materials/Methods: Setup data of 183 patients, divided into four different groups based on used setup devices, was used to calculate the difference between the predicted and the acquired treatment couch value. Results: Couch parameters can be predicted with high precision µ = 0.90 , σ = 0.92 . A significant difference (p < 0.01) between the variances of Lung and Brain patients was found. Outliers were not related to the prediction accuracy, but are due to inconsistencies during initial patient setup. Conclusion: Couch parameters can be predicted with high accuracy and can be used as starting point for SGRT-based patient positioning. In case of large deviations (>1.5 cm), patient setup has to be verified to optimally use the surface scanning system.

Comparing treatment uncertainty for ultra- vs. standard-hypofractionated breast radiation therapy based on in-vivo dosimetry.

Background and purpose: Postoperative ultrahypofractionated radiation therapy (UHFRT) in 5 fractions (fx) for breast cancer patients is as effective and safe as conventionally hypofractionated RT (HFRT) in 15 fx, liberating time for higher-level daily online Image-Guided Radiation Therapy (IGRT) corrections. In this retrospective study, treatment uncertainties occurring in patients treated with 5fx (5fx-group) were evaluated using electronic portal imaging device (EPID)-based in-vivo dosimetry (EIVD) and compared with the results from patients treated with conventionally HFRT (15fx-group) to validate the new technique and to evaluate if the shorter treatment schedule could have a positive effect on the treatment uncertainties. Materials and methods: EPID-based integrated transit dose images were acquired for each treatment fraction in the 5fx-group (203 patients) and on the first 3 days of treatment and weekly thereafter in the 15fx-group (203 patients). A total of 1015 EIVD measurements in the 5fx-group and 1144 in the 15fx-group were acquired. Of the latter group, 755 had been treated with online IGRT correction (i.e., Online-IGRT 15fx-group). Results: In the 15fx-group 12.0% of fractions failed (FFs) compared to 3.8% in the 5fx-group and 6.9% in the online-IGRT 15fx-group. Causes for FFs in the 15fx-group compared with the 5fx-group were patient positioning (7.4% vs. 2.2%), technical issues (3.1% vs. 1.2%) and breast swelling (1.4% vs. 0.5%). In the online-IGRT 15fx-group, 2.5% were attributed to patient positioning, 3.8% to technical issues and 0.5% to breast swelling. Conclusions: EIVD demonstrated that UHFRT for breast cancer results in less FFs compared to standard HFRT. A large proportion of this decrease could be explained by using daily online IGRT.