The Growing Burden of Cancer
The world is currently witnessing a worrying growth in new cancer diagnoses. 2020 brought about around 18.1 million new cases, a number which is set to inflate to 29.5 million in just under 20 years. This increase has beenattributed to three main factors: the growth of the world population, increased life expectancy, and changes in lifestyle.1
Indeed, the improved standard of medical care enjoyed by patients across the globe is leading to a growing number of cancer patients aged 65 or older. In 2020, this demographic accounted for 60% of all cancer patients registered in Europe. By 2050, this figure is set to grow to 65%, with half of the continent’s cancer patients being 75 or older.1
Whilst increased life expectancy as a result of improved cancer care is undoubtedly an encouraging sign of progress, this also means that the “typical cancer patients” of the very near future are the ones most likely to be excluded from clinical trials in the present day, primarily due to their generally “fragile” nature.
Radiation Therapy for Cancer: Where Are We Now?
In light of these circumstances, experts are now turning their gaze to new and improved technologies than can provide safer and more effective cancer care. In particular, significant efforts are focused on advancing radiation therapy for cancer treatment – one of the most widely used therapeutic modalities in oncology – to investigate how this can help mitigate some of the most pressing issues posed by the global cancer challenge.
Approximately 50% of all cancer patients undergo at least one course of radiotherapy throughout the course of their treatment journey. This figure reaches 87% in breast cancer patients. These numbers support the hypothesis that any significant developments in the field of radiotherapy are likely to benefit a substantial portion of cancer patients.
Adding to its benefits, radiotherapy is also widely considered as a “cost-effective” way of treating cancer. Nonetheless, this does not take away from the fact that the practice remains out of reach for many patients in Low and Middle Income Countries (LMICs), the very same territories that are expected to house around two-thirds of annual cancer cases by 2040.
With that being said, there is plenty of room for growth in the radiation therapy sphere. Recent research has predicted that sufficient investment in this clinical practice would give way for one million lives to be saved annually by 2035.2
Moreover, Schulz’s observation that the efficacy of radiation therapy for cancer has “reached a plateau”3 further highlights the need for a strong effort to continue improving the effectiveness of this therapeutic modality.
How Can We Improve Radiation Therapy for Cancer Patients?
Zeggini et al. identify three major anticancer translational strategies which, if implemented sufficiently, can serve to strengthen radiotherapy’s offering. These are as follows: primary prevention, early detection, and improved treatment.4 Baumann et al. suggest that the correct implementation of said strategies “will have a profound impact on the practice of radiation oncology in 2050”.1
Though primary prevention is a practice sure to benefit the healthcare ecosystem as a whole, its impact on the cancer radiotherapy sphere is anticipated to be especially significant.
Countries often lack sufficient radiotherapy treatment resources and professionals, regardless of their economic status. This is particularly significant in Asia, where industry shortages can be felt in LMICs of the likes of Sri Lanka and Bangladesh as well as in UMICs and HICs of the likes of Japan and South Korea. Furthermore, experts recommend that the training process for radiation oncology professionals should also include public health sciences and practical applications in a bid to help them “better utilise epidemiological data to plan their services and to cope appropriately with acute public health threats”.1
Zeggini et al.’s primary prevention strategy does have the potential of positively impacting the radiotherapy sphere, although its benefits will only be tangible many years down the line.4 Conversely, the widespread early detection of cancer is more likely to directly and tangibly impact radiation oncologists and the radiotherapy field as a whole. Most importantly, this would permit the use of specific radiotherapy techniques, such as stereotactic radiotherapy and brachytherapy for a wider spectrum of tumour sites than those that are currently being used.1
When it comes to the third and final anticancer translational strategy recommended by Zeggini et al. – improved cancer treatment – Baumann et al. note how, in recent years, major strides have been made in the development of safer and more efficient radiotherapy technologies. From sparing healthy tissue to more precise tumour imaging, recent developments in this sphere stand to show that radiotherapy is bound to remain a formative method of cancer treatment in the future.
In addition to these three strategies, Abdel-Wahab et al. identify a further three areas of improvement for radiotherapy: ‘education and training professionals’, ‘research’, and ‘advocacy and outreach’.2
Given the increasing incidence of cancer around the globe, the dynamic nature of radiotherapy technology, and the general shortage of radiotherapy professionals, Abdel-Wahab et al. emphasise the importance of accelerating both radiotherapy education as well as the training of new industry professionals. Testament to this is how, in developed countries, there are, on average, only two to three radiation oncologists for every 1,000 cancer patients. In LMICs, the situation is even more dire, with 0.76 radiation oncologists per 1,000 cancer patients in some regions.5
Furthermore, it is key that professionals in the field are given the opportunity to continuously update their knowledge in a bid to make way for the implementation of new and improved technologies. This situation can be further improved by introducing newly developed technologies to the clinic with lower personnel training requirements and shorter treatment times.
Research in the radiotherapy field goes beyond developing novel technologies or improving upon existing ones. Implementation research, for example, is particularly important, as it looks to address “the knowledge gap between evidence-based interventions and their delivery to community practice”. This could generate insights to facilitate the introduction of radiotherapy technologies to LMICs, where infrastructure and resources are lacking.
At present, most radiotherapy-related issues are addressed nationally or regionally, rather than globally. As a result of this, new technologies or findings are not always universally reproducible or relevant. This issue, in turn, serves to further alienate LMICs from the latest industry developments. Further collaboration between national and regional entities is required to combat this.
VHEE-RT: The Solution for Safe and Effective RT?
One of the notable developments in oncologic treatment, that has gained significant attention over the last two decades, concerns the possibility of using very high energy electrons (VHEE) – in the energy range of 100 to 250 MeV – in radiation therapy for cancer.8, 9 This has the potential bring about several advantages when compared to the use of high-energy photons – the most commonly used modality in clinics today.
Simulations, treatment planning studies and dose measurements with real beams using different irradiation schemes have consistently shown that not only can VHEE radiotherapy provide more accurate tumour targeting and therefore less damage to healthy tissues than photon radiotherapy,10, 11 but it is also “minimally affected by tissue heterogeneities” and “could be applicable in a large number of deep anatomical localisations”.6 Furthermore, VHEE radiotherapy is expected to be a drastically more cost-effective option, when compared to particle therapy techniques.
LPA Technology: The Best Way to Generate VHEE for Radiation Therapy?
In continued efforts to make VHEE-RT available to tomorrow’s patients, several research groups are now investigating different ways to reliably and cost-effectively generate focused VHEE beams in the ideal energy range to be used in radiation therapy for cancer.
One of the most promising approaches concerns the implementation of laser plasma (or laser wakefield) accelerator technology. Table-top laser wakefield accelerators were first proposed theoretically in the late 1970’s, and since then, remarkable progress has been made to develop this technology towards medical radiation treatment.12 Laser plasma accelerators have several advantages over conventional, RF-based accelerators for the generation of VHEEs for RT.
First, LPAs tend to be extremely compact, with a drastic reduction in the accelerating distance required, while also being more cost-effective. This would ensure that the next-generation RT equipment can fit into current treatment rooms with no infrastructure adjustments required. The enhanced compactness and portability, combined with reduced costs, gives a potential for wider implementation and availability, facilitating progress in improving treatment accessibility across the globe and especially in LMICs.
Thanks to many outstanding contributions, major strides have now been made in the development of this new and highly promising modality. Recent research suggests that therapeutic doses within localized volumes can already be obtained with existing LPA technology, calling for dedicated pre-clinical studies. In light of these benefits, Labate et al. highlight how “among all possible applications, exploitation of LPA sources in biology and medicine appears particularly appealing, in view of novel applications and protocols to be conceived and new devices deployed in medical practice”.7
Join the Ecosystem
Spearheaded by the Weizmann Institute of Science (WIS) and Acceler8 Venture Builder (A8), the EIC-funded eBeam4Therapy project is working on demonstrating an innovative, safe, and cost-effective cancer radiotherapy approach based on electrons which are given very high energies using laser plasma accelerator technology.
The final aim of eBeam4Therapy is to create a cost-effective and highly accessible form of radiotherapy, with lower irradiation effects on the adjacent healthy tissues and organs.
Cancer care aside, the eBeam4Therapy team is also considering the possibility of applying the advanced LPA technologies to a growing variety of sectors, such as isotope production and non-destructive testing.
Interested in this Technology?
We’re working on establishing an ecosystem around VHEE technologies. Should you be interested in this topic, work with radiation therapy for cancer, or have something to contribute, drop us a message through our social channels.
In the meantime, make sure to sign up to our quarterly newsletter at ebeam4therapy.eu to be kept updated with the project’s most pressing developments.
REFERENCES
[1] Baumann, M., Ebert, N., Kurth, I., Bacchus, C., & Overgaard, J. (2020). What will radiation oncology look like in 2050? A look at a changing professional landscape in Europe and beyond. Molecular Oncology, 14(7), 1577–1585. https://doi.org/10.1002/1878-0261.12731
[2] Abdel-Wahab, M., Gondhowiardjo, S. S., Rosa, A. A., Lievens, Y., El-Haj, N., Polo Rubio, J. A., Prajogi, G. B., Helgadottir, H., Zubizarreta, E., Meghzifene, A., Ashraf, V., Hahn, S., Williams, T., & Gospodarowicz, M. (2021). Global Radiotherapy: Current Status and Future Directions—White Paper. JCO Global Oncology, 7, 827–842. https://doi.org/10.1200/go.21.00029
[3] Schulz, R. J. (2021). The future of radiation therapy. Journal of Applied Clinical Medical Physics, 22(1), 350–350. https://doi.org/10.1002/acm2.13141
[4] Zeggini, E., Baumann, M., Götz, M., Herzig, S., Hrabe De Angelis, M., & Tschöp, M. H. (2020). Biomedical Research Goes Viral: Dangers and Opportunities. Cell, 181(6), 1189–1193. https://doi.org/10.1016/j.cell.2020.05.014
[5] Grand View Research. (2023). Radiation Oncology Market Size, Share & Trends Analysis Report By Type (External Beam Radiation Therapy, Internal Beam Radiation Therapy), By Technology, By Application, By Region, And Segment Forecasts, 2023 – 2030. In Grand View Research. https://www.grandviewresearch.com/industry-analysis/radiation-oncology-market
[6] Ronga, M. G., Cavallone, M., Patriarca, A., Leite, A. M., Loap, P., Favaudon, V., Créhange, G., & De Marzi, L. (2021). Back to the Future: Very High-Energy Electrons (VHEEs) and Their Potential Application in Radiation Therapy. Cancers, 13(19), 4942. https://doi.org/10.3390/cancers13194942
[7] Labate, L., Palla, D., Panetta, D., Avella, F., Baffigi, F., Brandi, F., Di Martino, F., Fulgentini, L., Giulietti, A., Köster, P., Terzani, D., Tomassini, P., Traino, C., & Gizzi, L. A. (2020). Toward an effective use of laser-driven very high energy electrons for radiotherapy: Feasibility assessment of multi-field and intensity modulation irradiation schemes. Scientific Reports, 10(1). https://doi.org/10.1038/s41598-020-74256-w
[8] DesRosiers, C., Moskvin, V., Bielajew, A. F., & Papiez, L. (2000). 150-250 MeV electron beams in radiation therapy. Physics in Medicine and Biology, 45(7), 1781–1805. https://doi.org/10.1088/0031-9155/45/7/306
[9] Yeboah, C., Sandison, G. A., & Moskvin, V. (2002). Optimization of intensity-modulated very high energy (50–250 MeV) electron therapy. Physics in Medicine and Biology, 47(8), 1285–1301. https://doi.org/10.1088/0031-9155/47/8/305
[10] Kokurewicz, K., Brunetti, E., Welsh, G. I., Wiggins, S., Boyd, M., Sorensen, A., Chalmers, A. J., Schettino, G., Subiel, A., DesRosiers, C., & Jaroszynski, D. A. (2019). Focused very high-energy electron beams as a novel radiotherapy modality for producing high-dose volumetric elements. Scientific Reports, 9(1). https://doi.org/10.1038/s41598-019-46630-w
[11] Svendsen, K., Guenot, D., Svensson, J., Petersson, K., Persson, A., & Lundh, O. (2021). A focused very high energy electron beam for fractionated stereotactic radiotherapy. Scientific Reports, 11(1). https://doi.org/10.1038/s41598-021-85451-8
[12] Chiu, C. Y., Fomyts’kyi, M., Grigsby, F., Raischel, F., Downer, M. C., & Tajima, T. (2004). Laser electron accelerators for radiation medicine: A feasibility study. Medical Physics, 31(7), 2042–2052. https://doi.org/10.1118/1.1739301