Search

BackgroundState-of-the-art radiotherapy of locally advanced non-small cell lung cancer (LA-NSCLC) is performed with intensity-modulation during free breathing (FB). Previous studies have found encouraging geometric reproducibility and patient compliance of deep inspiration breath hold (DIBH) radiotherapy for LA-NSCLC patients. However, dosimetric comparisons of DIBH with FB are sparse, and DIBH is not routinely used for this patient group. The objective of this simulation study was therefore to compare DIBH and FB in a prospective cohort of LA-NSCLC patients treated with intensity-modulated radiotherapy (IMRT).MethodsFor 38 LA-NSCLC patients, 4DCTs and DIBH CTs were acquired for treatment planning and during the first and third week of radiotherapy treatment. Using automated planning, one FB and one DIBH IMRT plan were generated for each patient. FB and DIBH was compared in terms of dosimetric parameters and NTCP. The treatment plans were recalculated on the repeat CTs to evaluate robustness. Correlations between ΔNTCPs and patient characteristics that could potentially predict the benefit of DIBH were explored.ResultsDIBH reduced the median Dmean to the lungs and heart by 1.4 Gy and 1.1 Gy, respectively. This translated into reductions in NTCP for radiation pneumonitis grade ≥2 from 20.3% to 18.3%, and for 2-year mortality from 51.4% to 50.3%. The organ at risk sparing with DIBH remained significant in week 1 and week 3 of treatment, and the robustness of the target coverage was similar for FB and DIBH. While the risk of radiation pneumonitis was consistently reduced with DIBH regardless of patient characteristics, the ability to reduce the risk of 2-year mortality was evident among patients with upper and left lower lobe tumors but not right lower lobe tumors.ConclusionCompared to FB, DIBH allowed for smaller target volumes and similar target coverage. DIBH reduced the lung and heart dose, as well as the risk of radiation pneumonitis and 2-year mortality, for 92% and 74% of LA-NSCLC patients, respectively. However, the advantages varied considerably between patients, and the ability to reduce the risk of 2-year mortality was dependent on tumor location. Evaluation of repeat CTs showed similar robustness of the dose distributions with each technique.

Radiation therapy using protons and heavier ions is a fast-growing therapeutic option for cancer patients. A clinical system for particle imaging in particle therapy would enable online patient position verification, estimation of the dose deposition through range monitoring and a reduction of uncertainties in the calculation of the relative stopping power of the patient. Several prototype imaging modalities offer radiography and computed tomography using protons and heavy ions. A Digital Tracking Calorimeter (DTC), currently under development, has been proposed as one such detector. In the DTC 43 longitudinal layers of laterally stacked ALPIDE CMOS monolithic active pixel sensor chips are able to reconstruct a large number of simultaneously recorded proton tracks. In this study, we explored the capability of the DTC for helium imaging which offers favorable spatial resolution over proton imaging. Helium ions exhibit a larger cross section for inelastic nuclear interactions, increasing the number of produced secondaries in the imaged object and in the detector itself. To that end, a filtering process able to remove a large fraction of the secondaries was identified, and the track reconstruction process was adapted for helium ions. By filtering on the energy loss along the tracks, on the incoming angle and on the particle ranges, 97.5% of the secondaries were removed. After passing through 16 cm water, 50.0% of the primary helium ions survived; after the proposed filtering 42.4% of the primaries remained; finally after subsequent image reconstruction 31% of the primaries remained. Helium track reconstruction leads to more track matching errors compared to protons due to the increased available focus strength of the helium beam. In a head phantom radiograph, the Water Equivalent Path Length error envelope was 1.0 mm for helium and 1.1 mm for protons. This accuracy is expected to be sufficient for helium imaging for pre-treatment verification purposes.

Manual volumetric modulated arc therapy (VMAT) treatment planning for high-risk prostate cancer receiving whole pelvic radiotherapy (WPRT) with four integrated dose levels is complex and time consuming. We have investigated if the radiotherapy planning process and plan quality can be improved using a well-tuned model developed through a commercial system for knowledge-based planning (KBP). Treatment plans from 69 patients treated for high-risk prostate cancer with manually planned VMAT were used to develop an initial KBP model (RapidPlan, RP). Prescribed doses were 50, 60, 67.5, and 72.5 Gy in 25 fractions to the pelvic lymph nodes, prostate and seminal vesicles, prostate gland, and prostate tumour(s), respectively. This RP model was in clinical use from July 2019 to February 2020, producing another set of 69 clinically delivered treatment plans for a new patient group, which were used to develop a second RP model. Both models were validated on an independent group of 40 patients. Plan quality was compared by D98% and the Paddick conformity index for targets, mean dose (Dmean) and generalised equivalent uniform dose (gEUD) for bladder, bowel bag and rectum, and number of monitor units (MU). Target coverage and conformity was similar between manually created and RP treatment plans. Compared to the manually created treatment plans, the final RP model reduced average Dmean and gEUD with 2.7 Gy and 1.3 Gy for bladder, 1.2 Gy and 0.9 Gy for bowel bag, and 2.7 Gy and 0.8 Gy for rectum, respectively (p < .05). For rectum, the interpatient variation (i.e., 95% confidence interval) of DVHs was reduced by 23%. KBP improved plan quality and consistency among treatment plans for high-risk prostate cancer. Model tuning using KBP-based clinical plans further improved model outcome.

Cancer is a destructive disease, in which tumor cells grow out-of-control, halting organ function. Its treatment is threefold: Radical surgery, chemotherapy and radiation therapy. Their relative usage is determined by cancer type, stage, organs at risk adjacent to the tumor and progression. There has been a significant increase in the number of cancer patients treated with radiation therapy using particle therapy in the recent decades worldwide. Short term and long term treatment-induced side effects are reduced when applying particle therapy due to the superior dose conformality compared to conventional radiation therapy using photons. The particle species commonly applied during particle therapy is the proton. Proton therapy as of today is performed with the delivery of pre-calculated dose plans for each patient: the applied dose plans are made based on x-ray computed tomography (CT) images. The CT images are reconstructed based upon photon interaction with matter, thus a conversion is required for calculating the Relative Stopping Power for how the protons traverse and deposit dose in the patient’s body during proton therapy. This conversion procedure introduces range uncertainties typically in the order of 2%–3%, corresponding to 4–6 mm at a treatment depth 20 cm into the patient. A proton CT system would yield a means of direct calculation of the RSP map in the patient. During a proton CT scan, a high-energy proton beam is directed at the patient and the proton beam must have sufficient energy to completely pass through the patient being imaged. The protons’ residual energies are measured after they have traversed through the patient and into a detector behind to the patient. The information about the residual energy from each proton can then be used, together with the proton’s estimated path through the patient, as a basis for reconstructing a volumetric RSP. In this thesis, the feasibility of using a purely pixel-based detector, a so-called Digital Tracking Calorimeter (DTC), for proton CT purposes is investigated and its performance quantified through experiments and Monte Carlo simulations. The DTC is designed for tracking and measuring the range and energy of individual protons in a proton beam. The DTC consists of multiple layers of semiconductor pixel sensors with a digital readout, interleaved with a passive absorber material for energy degradation. The sensor chips are considered near optimal for use in the tracking, due to their data processing capacity at the required readout speed, the high granularity of such a detector system and also due to their short radiation thickness. The requirement to this part of the detector is that it must be able to allow for reconstruction of a large amount of proton tracks in each data readout cycle, enabling high proton rate capabilities. The DTC was originally designed for the reconstruction of high-energy electromagnetic showers for the Forward Calorimeter project in the ALICE experiment at CERN. The presented prototype forms the basis for a proton CT system using a single pixelbased technology for both tracking and calorimetry. This advantage simplifies the setup and reduces the cost of a proton CT system assembly, and it is a unique feature of the Digital Tracking Calorimeter concept. Measurement data from the AGORFIRM beamline at KVI-CART in Groningen in the Netherlands and Monte Carlo simulation results are used in order to develop a proton tracking algorithm for the estimation of the residual ranges of a high number of concurrent proton tracks. The range of the individual protons can with the first prototype be estimated with a range resolution of 6–25 mm Water Equivalent Thickness. This relatively low achieved range resolution is expected due to the original design goal of the prototype. The readout system for this prototype is able to handle a proton intensity of 1 million protons/s by using 500 concurrent proton tracks in each readout frame, which is comparable to present similar prototypes. A next prototype of the proton CT setup using the DTC is at present in the construction stage. A DTC further optimized for use in a proton CT system will utilize next-generation Monolithic Active Pixel Sensors with larger sensor areas and a hundredfold increase in readout speeds. The developed proton CT analysis framework is applied on a variety of possible DTC geometries for the next prototype. The potential design choices are evaluated on basis of the reached range accuracy and range uncertainty as well as of the track reconstruction efficiency. A design recommendation is reached where the proposed DTC will have 3.5 mm thick aluminum absorber slabs between each sensor layer. Some of the tools applied in this thesis for the purpose of proton range calculation have been validated through comparison studies: First, different MC programs are compared to each other and to available experimental data. Secondly, the accuracy and usability of several available proton range calculation models are evaluated through their capability of reproducing tabulated energy-range proton values. An accurate model is found and applied throughout this thesis for proton range reconstruction purposes.

In this thesis, we explore the phenomenological minimal supersymmetric standard model (pMSSM) in the context of the Higgs boson. If the emerging results from the LHC are real, will the pMSSM be able to accommodate this? We perform scans over the parameter space of pMSSM, calculate different observables and compare them to the experimental constraints available. We find the models which pass all the constraints, and compare these to the results from the LHC using the newest data. Based on this, we find that they are incompatible, albeit with a low significance. Master i Fysikk MAMN-PHYS PHYS399

Introduksjon: Intensitetsmodulert protonterapi (IMPT) kan potensielt gi betre behandling av lokalavansert ikkje-småcella lungekreft (LA-NSCLC) samanlikna med intensitetsmodulert stråleterapi (IMRT) med foton, som er dagens "state-of-the-art". Proton har meir avgrensa doseavsetning og betre sparing av normalvev, men sidan rekkevidda til protona er svært sensitiv til tettleiksendringar, er behandling i lungeregionen spesielt utfordrande. Dette på grunn av pustebevegelsar og anatomiske endringar. Det er behov for adaptive protokollar, kor analyse av den vatn-ekvivalente rekkevidda (WEPL) til protona i pasienten kan vere eit nyttig hjelpemiddel. Målet med denne studien var å evaluere nytta av WEPL i adaptiv protonterapi av LA-NSCLC ved å studere korrelasjonen mellom WEPL-endringar og degradering av dose til målvolumet. Material og metode: Bilete og IMPT-planar for 15 pasientar med LA-NSCLC blei inkludert i denne retrospektive studien. Pasientane blei behandla med IMRT på Haukeland Universitetssjukehus, og robust optimerte IMPT-planar blei laga i etterkant. CT-bilete blei tekne for planlegging (pCT) og repeterte (rCT) i veke 1 og veke 3 av behandlingsløpet. Ein pasient tok ikkje rCT i veke 3, så 29 rCT-bilete var tilgjengelege. IMPT-planane blei rekalkulert på rCT-bileta, og volumandelen av det kliniske målvolumet (CTV) som mottek minst 95% av den planlagde dosen (V95) blei henta ut. For å rekne ut WEPL i CT-bileta måtte det ei kalibrering til, der CT-tala blei oversett til den relative stoppekrafta (RSP) av proton, karakteristisk for den brukte CT-maskina. For kvar pasient blei WEPL kalkulert til alle punkt i bakkanten av CTV-strukturen i pCT-biletet og i rCT-bileta. Endringa i WEPL (ΔWEPL) frå pCT til rCT blei samanlikna med endringa i CTV V95 (ΔV95) frå den originale IMPT-planen til rekalkuleringa på rCT. Endringar i WEPL blei kvantifisert som gjennomsnittet og 95-percentilen av |ΔWEPL| samt prosentandelen punkt i bakkanten av CTV med > 10 mm og > 3 mm WEPL-endringar. Resultat: Med kalibreringa kunne RSP-verdiar predikerast med ein relativ feil på 4.6% og brukast til å rekne ut WEPL i CT-bileta av pasientane. Medianen av gjennomsnittleg |ΔWEPL| for alle pasientar var 5.4 mm i veke 1 og 4.5 mm i veke 3, og medianen for prosentandelen punkt med ΔWEPL | >10 mm var 13.1% i veke 1 og 10.0% i veke 3. Statistisk signifikant korrelasjon (p < 0.05) blei funnen mellom ΔV95 og prosentandelen punkt med ΔWEPL 10 mm and > 3 mm WEPL changes. Results: With the obtained calibration curve, RSP values were predicted with a mean relative error of 4.6% and were used to calculate the WEPL in the patient CT scans. The median of the mean |ΔWEPL| for all patients was 5.4 mm in week 1 and 4.5 mm in week 3, and the median percentage of pixels at the distal edge of CTV with |ΔWEPL| > 10 mm was 13.1% in week 1 and 10.0% in week 3. There was a statistically significant correlation (p < 0.05) between the ΔV95 and the percentage of points with ΔWEPL < -10 mm, being the only tested parameter with correlation. Seven of the 29 recalculated IMPT plans had ΔV95 < -1%. The ΔWEPL was not significantly different for these than for the plans with less target dose degradation (p>0.05). Conclusion: In this study, changes in WEPL to the distal edge of the CTV did not correlate with changes in CTV V95. The WEPL is not a feasible tool in adaptive proton therapy of LA-NSCLC with robust optimised IMPT plans.