Visiting Professor Manjit Dosanjh

Abstract:

BACKGROUND: FLASH radiotherapy has emerged as a promising advancement in radiation oncology, demonstrating the potential to minimize normal tissue toxicity while preserving tumoricidal efficacy. However, the precise beam parameters required for clinical translation remain to be fully defined. METHODS: To optimize beam parameters for clinical application, we employed Very High Energy Electrons (VHEE) at the CLEAR facility, capable of targeting deep-seated tumors. These were used alongside a FLASH-validated Intermediate Energy Electron (IIE) beam and a 160-225 keV X-ray beam, collectively delivering dose rates from 1 Gy/min to 1011 Gy/s. High-throughput chemical assays investigated the radiochemical effects across this dose rate range, while zebrafish embryos provided an in vivo model to evaluate biological responses and developmental outcomes. This study offers the first comprehensive analysis of FLASH effects across a wide spectrum of dose rates and temporal parameters, from early physico-chemical interactions to complex biological systems. RESULTS: Data from CLEAR demonstrated that beam intensity, particularly bunch charge, is a critical determinant of the FLASH effect, and uncovered an unforeseen biological response when electrons are delivered over the picosecond timescale. CONCLUSION: Our findings suggest that scanning strategies employing high intensity beamlets may be optimal for the clinical implementation of FLASH radiotherapy. These insights are pivotal for guiding the development of future FLASH protocols in radiation oncology.

Abstract:

The battle against cancer remains a top priority for society, with an urgent need to develop therapies capable of targeting challenging tumours while preserving patient's quality of life. Hadron Therapy (HT), which employs accelerated beams of protons, carbon ions, and other charged particles, represents a significant frontier in cancer treatment. This modality offers superior precision and efficacy compared to conventional methods, delivering therapeutic the dose directly to tumours while sparing healthy tissue. Even though 350,000 patients have already been treated worldwide with protons and 50,000 with carbon ions, HT is still a relatively young field and more research as well as novel, cost-effective and compact accelerator technologies are needed to make this treatment more readily available globally. Interestingly the very first patient was irradiated with protons in September 1954, the same month and year CERN was founded. Both of these endeavours are embedded in cutting edge technologies and multidisciplinary collaboration. HT is finally gaining ground and, even after 70 years, the particle therapy field continues innovating and improving for the benefits of patients globally. Developing technologies that are both affordable and easy to use is key and would allow access to more patients. Advances in accelerator-driven Boron Neutron Capture Therapy (BNCT), image-guided hadron beams delivery, clinical trials and immunotherapy, together with the recent interest and advances in FLASH therapy, which is currently an experimental treatment modality that involves ultrahigh-dose rate delivery, are just a few examples of innovation that may eventually help to provide access to a larger number of patients.

Abstract:

Objective.To evaluate spatially fractionated radiation therapy (SFRT) for very-high-energy electrons (VHEEs) delivered with pencil beam scanning.Approach. Radiochromic film was irradiated at the CERN linear electron accelerator for research using 194 MeV electrons with a step-and-shoot technique, moving films within a water tank. Peak-to-valley dose ratios (PVDRs), depths of convergence (PVDR ⩽ 1.1), peak doses, and valley doses assessed SFRT dose distribution quality. A Monte Carlo (MC) model of the pencil beams was developed using TOPAS and applied to a five-beam VHEE SFRT treatment for a canine glioma patient, compared to a clinical 6 MV VMAT plan. The plans were evaluated based on dose-volume histograms, mean dose, and maximum dose to the planning target volume (PTV) and organs at risks (OARs).Main results. Experimental PVDR values were maximized at 15.5 ± 0.1 at 12 mm depth for 5 mm spot spacing. A DOC of 76.5, 70.7, and 56.6 mm was found for 5, 4, and 3 mm beamlet spacings, respectively. MC simulations and experiments showed good agreement, with maximum relative dose differences of 2% in percentage depth dose curves and less than 3% in beam profiles. Simulated PVDR values reached 180 ± 4, potentially achievable with reduced leakage dose. VHEE SFRT plans for the canine glioma patient showed a decrease in mean dose (>16%) to OARs while increasing the PTV mean dose by up to 15%. Lowering beam energy enhanced PTV dose homogeneity and reduced OAR maximum doses.Significance. The presented work demonstrates that pencil beam scanning SFRT with VHEEs could treat deep-seated tumors such as head and neck cancer or lung lesions, though small beam size and leakage dose may limit the achievable PVDR.

Abstract:

<h4>Background</h4>Only 10-40% of patients with cancer in low-income and middle-income countries were able to access curative or palliative radiotherapy in 2015. We aimed to assess the current status of diagnostic imaging and radiotherapy services in the Baltic countries, eastern Europe, central Asia, and the Caucasus by collecting and analysing local data.<h4>Methods</h4>This Access to Radiotherapy (ART) comprehensive analysis used data from 12 countries: the three Baltic countries (Estonia, Latvia, and Lithuania), two countries in eastern Europe (Moldova and Ukraine), four countries in central Asia (Kazakhstan, Kyrgyzstan, Tajikistan, and Uzbekistan), and three countries in the Caucasus (Armenia, Azerbaijan, and Georgia), referred to here as the ART countries. We were not able to obtain engagement from Turkmenistan. The primary outcome was to update the extent of shortfalls in the availability of diagnostic imaging and radiotherapy technologies and radiotherapy human resources for patients with cancer in former Soviet Union countries. Following the methods of previous similar studies, we developed three questionnaires-targeted towards radiation oncologists, regulatory authorities, and researchers-requesting detailed information on the availability of these resources. Authors from participating countries sent two copies of the appropriate questionnaire to each of 107 identified institutions and coordinated data collection at the national level. Questionnaires were distributed in English and Russian and responses in both languages were accepted. Two virtual meetings held on May 30 and June 1, 2022, were followed by an in-person workshop held in Almaty, Kazakhstan, in September, 2022, attended by representatives from all participating countries, to discuss and further validate the data submitted up to this point. The data were collected on a dedicated web page, developed by the International Cancer Expert Corps, and were then extracted and analysed.<h4>Findings</h4>Data were collected between May 10 and Nov 30, 2022. 81 (76%) of the 107 institutions contacted, representing all 12 ART countries, submitted 167 completed questionnaires. The Baltic countries, which are defined as high-income countries, had more diagnostic imaging equipment and radiotherapy human resources (eg, Latvia [1·74] and Lithuania [1·47] have a much higher number of radiation oncologists per 100 000 population than the other ART countries, all of which had <1 radiation oncologist per 100 000 population) and greater radiotherapy technological capacities (higher numbers of linear accelerators and, similar to Georgia, high total external beam radiotherapy capacity) than the other ART countries, as well as high cancer detection rates (Latvia 311 cases per 100 000 population, Lithuania 292, and Estonia 288 vs, for example, 178 in Armenia, 144 in Ukraine, and 72 in Kazakhstan) and low cancer mortality-to-cancer incidence ratios (Estonia 0·43, Latvia 0·49, and Lithuania 0·48; lower than all but Kazakhstan [0·41]). The highest cancer mortality-to-cancer incidence ratios were reported by Moldova (0·71) and Georgia (0·74).<h4>Interpretation</h4>Our findings show that the number of cancer cases, availability of diagnostic imaging equipment, radiation oncologists and radiotherapy capacity, and cancer mortality-to-cancer incidence ratios all vary substantially across the countries studied, with the three high-income, well resourced Baltic countries performing better in all metrics than the included countries in eastern Europe, central Asia, and the Caucasus. These data highlight the challenges faced by many countries in this study, and might help to justify increased investment of financial, human, and technological resources, with the aim to improve cancer treatment outcomes.<h4>Funding</h4>US Department of Energy's National Nuclear Security Administration's Office of Radiological Security.

Abstract:

There has long existed a substantial disparity in access to radiotherapy globally. This issue has only been exacerbated as the growing disparity of cancer incidence between high-income countries (HIC) and low and middle-income countries (LMICs) widens, with a pronounced increase in cancer cases in LMICs. Even within HICs, iniquities within local communities may lead to a lack of access to care. Due to these trends, it is imperative to find solutions to narrow global disparities. This requires the engagement of a diverse cohort of stakeholders, including working professionals, non-governmental organizations, nonprofits, professional societies, academic and training institutions, and industry. This review brings together a diverse group of experts to highlight critical areas that could help reduce the current global disparities in radiation oncology. Advancements in technology and treatment, such as artificial intelligence, brachytherapy, hypofractionation, and digital networks, in combination with implementation science and novel funding mechanisms, offer means for increasing access to care and education globally. Common themes across sections reveal how utilizing these new innovations and strengthening collaborative efforts among stakeholders can help improve access to care globally while setting the framework for the next generation of innovations.