published_or_final_version / Clinical Oncology / Master / Master of Research in Medicine

Materials/Methods: Ten patients who underwent thoracic SBRT with primary stage I (T1/2N0) lung cancer or oligometastatic lung lesion, with PTV diameter ≤ 5cm were selected and were immobilized with Easyfoam or Vac-Lock. Planned/treated with inspiratory breath-hold (25 seconds, 70 to 80% of vital capacity) assisted with Active Breathing Control (ABC). Four treatment plans: non-coplanar 3DCRT, coplanar static gantry IMRT, coplanar VMAT (FF) and VMAT (FFF) were generated. Field arrangements, either static fields or partial arcs (duration=20 sec) were used to avoid direct beam entry to contralateral lung. All plans were compared in terms of dosimetric performance included dose to PTV or organs at risk (OAR), high/low dose spillage, integral dose (body and lungs), dose delivery efficiency (MU/Gy) and estimated beam-on time (BOT) with reference to the RTOG 0813 protocol. Results: All plans complied with RTOG 0813 protocol. VMAT (FF/ FFF) techniques improved target coverage and dose conformity, with the highest conformity number (CN > 0.91), compared to IMRT (0.88) and 3DCRT (0.85). The control of high dose spillage (NT>105% and CI) for IMRT (3.04% and 1.08) and VMAT (FF/ FFF) (1.08/ 1.06% and 1.03/ 1.04) techniques were comparable (p > 0.05) and significantly better than 3DCRT (4.22% and 1.11, p < 0.005) technique. In addition, VMAT (FF/ FFF) techniques performed the best in controlling low dose spillage (D2cm and R50%) compared with IMRT (reduction: 4.7%, p=0.036 and >5.9%, p = 0.009) and 3DCRT (reduction: > 16.3%, p < 0.001 and > 10%, p = 0.002). Benefits of rapid and isotropic dose fall-off were shown from superior tissue sparing (reduction ranges from 3.2% up to 67%) of ipsilateral brachial plexus, skin (0-5mm), great vessels and ribs. Also lung V10, V12.5, esophagus and heart tend to receive lower dose with VMAT technique. The relatively lower integral dose to whole body (> 3Gy∙L reduction, p < 0.013) and ipsilateral lung (0.65Gy∙L reduction, p = 0.025) compared with 3DCRT, were associated with lower risk of radiation induced cancers. The MU/Gy and BOT were substantial lower for VMAT (FF) (22.4% and 32.4%) compared with IMRT. Apart from higher (7%) maximum skin dose, dosimetric performance for VMAT (FFF) was comparable with VMAT (FF), with advantages of further reduction of MU/Gy (1.8% lesser), partial arc numbers (from 12-14 arcs down to 8 arcs) and BOT (35% shortened), owing to the increased dose output with flattening filter removal. Conclusions: VMAT (FF and FFF) plans maintained IMRT equivalent plan qualities, simultaneously enhanced the delivery efficiency with shortened BOT. VMAT (FFF) further reduced the required arcs number and BOT, significantly minimized the intra-fraction motions and more tolerable to patient with long SBRT treatment duration. / published_or_final_version / Medicine / Master / Master of Medical Sciences

Stereotactic body radiotherapy (SBRT) is a promising treatment strategy for early–stage lung cancers. Conventional three–dimensional (3D) SBRT based on a static patient geometry is an insufficient model of reality, posing constraints on accurate Monte Carlo (MC) dose calculation and intensity–modulated radiotherapy (IMRT) optimization. Four–dimensional (4D) radiotherapy explicitly considers temporal anatomical changes by characterizing the organ motion and building a 4D patient model, generating a treatment plan that optimizes the doses to moving tissues, i.e., 4D dose (as opposed to the static 3D dose to tissue), and delivering this plan by synchronizing the radiation with the moving tumor. This thesis focuses on 4D robotic tracking lung SBRT. By recalculating the conventional 3D plan on the 4D patient model using MC simulation, it was found that 4D moving dose distributions could detect increase of normal tissue doses and complication probabilities (NTCP), and decrease of tumor dose and control probability. For one patient, the risk of myelopathy was estimated at 8% and 18% from the 3D equivalent path–length corrected (EPL) and the 4D MC doses, respectively. Such increased NTCP suggests that better estimations of different dosimetric quantities using 4D MC dose calculation are crucial to improve the existing dose–response models. Dosimetric error in 4D robotic tracking SBRT was found to be caused predominately by tissue heterogeneities, as assessed by the comparisons of the 4D moving tissue doses calculated using the conventional EPL and MC algorithms. At 3% tolerance level, our results indicated clinically significant dose prediction errors only in tumor but not in other major normal tissues. Furthermore, 4D tracking radiotherapy was found to have greater ability to limit the normal tissue volume receiving high to medium doses than the other advanced SBRT strategy combining volumetric–arc radiotherapy with 4D cone–beam CT verification. Invariant target motion was found to be an unrealistic assumption of 4D radiotherapy from the analysis of probability motion function (pmf) of motion data. Systematic and random variations of motion amplitude, frequency, and baseline were found to reduce the reproducibility of pmfs, on average, to just 30% for the principal motion of 3400 seconds. Experimental evaluations showed that systematic motion change reduced the gamma passing rate of radiochromic film measurements at 3mm distance–to–agreement and 3% dose difference criteria from 91% for 4D dose calculated with MCand EPL algorithms to 47% and 53% in the static object, respectively,. For moving target object, gamma passing rates of the 4D MC doses hardly changed with reproducible and non–reproducible motion (95% vs. 93%), and barely differed between conventional 3D and 4D MC doses (95% vs. 95% with reproducible, and 96% vs. 93% with non–reproducible motions). Distortions due to image artifacts and registration errors were consistently observed in the 4D dose distributions but not the 3D dose distributions. In conclusion, 4D Monte Carlo planning shall be considered for robotic target tracking only if robustness against uncertainties of patient geometry, and accuracy of 4DCT imaging and deformation registration are significantly improved. / published_or_final_version / Clinical Oncology / Doctoral / Doctor of Philosophy

Purpose: The aim of the study is to compare the positioning accuracy of two immobilization systems commonly used in stereotactic body radiation therapy (SBRT) of non–small cell lung carcinoma (NSCLC) and lung oligometastases, Polyurethane Foam Cradles (PFC) and the BodyFIX System (BFS) with 2D and 3D image guidance. Both the interfraction and intrafractional positional errors were analyzed. Methods and Materials: 189 CBCT scans from 44 patients with NSCLC or lung oligometastases who received SBRT between August 2008 and April 2014 were analyzed retrospectively. Of these, 20 and 24 patients were immobilized with a Polyurethane Foam Cradle (PFC) and the BodyFIX System (BFS) respectively. The results of on board imaging (OBI) and pre-treatment cone-beam computed tomography (CBCT) at initial setup and after correction were registered to planning CT for online matching. The positional errors in anteroposterior (AP), superior-inferior (SI) and medial-lateral (ML) directions were analyzed. Post-treatment CBCT were used to assess intrafraction tumour displacement for 19 patients. The planning target volume margins were calculated using the van Herk’s formula. Other possible factors contributing to setup uncertainty were also analyzed. Result: By using skin mark as a reference, the mean setup errors were 0.09, -0.10 and 0.02 cm for PFC and 0.04, -0.19 and -0.10 cm for BFS in AP, SI and ML directions respectively. The mean setup errors were decreased to 0.04, 0.02 and 0.04 cm for PFC; and -0.04, -0.04 and -0.02 cm for BFS after the application of OBI. The errors were further decreased to below 0.02 cm in all directions after the application of first pre-treatment CBCT in both immobilization methods. Statistically significant difference (p < 0.05 ) was only found in the comparison of AP error between the two devices, when OBI was used as the verification method. For PFC, the 3D vector errors of skin mark, OBI and first pre-treatment CBCT were 6.4 mm, 2.9 mm and 0.5 mm, respectively cases. For BFS, the errors were 7.1 mm, 3.0 mm and 0.4 mm, respectively. Smaller PTV margins in various directions were needed in BFS when using CBCT as the verification method. Positioning errors of skin mark setup in AP and SI directions had major contributions to all the setup errors; gender and tumour location might significantly affect the setup uncertainties. Comparatively large intrafractional errors were found in the post-treatment CBCT results of PFC. Conclusion: When employing the CBCT-based final couch position as the benchmark, the setup errors of skin mark, OBI and first CBCT results were compared relatively. The positioning accuracies of PFC and BFS were similar. Apart from the vertical error (AP direction) found in the OBI verification, there was no significant difference between the positioning accuracy of both immobilization devices. Both imaging guided RT techniques were superior to skin mark. OBI and CBCT online correction improved the positioning accuracy of lung SBRT and substantially reduces required target margins and normal tissue irradiation. / published_or_final_version / Diagnostic Radiology / Master / Master of Medical Sciences

No description available.

published_or_final_version / Nursing Studies / Master / Master of Nursing in Advanced Practice

D.Tech. (Biomedical Technology) / Photodynamic therapy (PDT) is an alternative treatment modality for malignant tumours based on the photodamage to tumour cells through a photochemical reaction (Ahn et al., 2013). PDT utilizes a light sensitive photosensitizer (PS) that selectively localizes in tumour cells and is excited by light of a specific wavelength in the presence of molecular oxygen. The excited PS leads to the generation of singlet oxygen or other reactive oxygen species(ROS) which induces cytotoxic damage to cellular organelles and eventually cell death. Singlet oxygen has a very short life and its generation is controlled by the presence of the PS and the laser light (Senge and Radomski, 2013).The subcellular localization site of the PS plays a vital role in determining the effectiveness and the extent of cellular damage as well as the mechanism involved in cell death. Lung cancer is the leading cause of cancer death worldwide in both males and females, with an estimated 1.4 million deaths each year (American Cancer Society, 2011). Therapeutic modalities used in the treatment of lung cancer such as chemotherapy, radiotherapy and immunotherapy have rarely yielded a good prognosis and effective treatment remains a challenging problem to date. An alternative treatment modality with minimal complications such as PDT needs to be explored. Most in vitro PDT experiments are conducted on monolayer cultures and the cellular environment of these cultures does not correspond to that of in vivo studies. Multicellular tumour spheroids (MCTSs) serves as an important model in cancer research for the evaluation of therapeutic interventions since they mimic different aspects of the human tumour tissue environment.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / abstract / Clinical Oncology / Doctoral / Doctor of Philosophy