This study was based on a survey to investigate perceptions of hadrontherapy of the members of the Italian Association of Medical Physics (AIFM). The survey was digitally submitted to the 991 members between the end of January and the beginning of April 2016.
A 19-item questionnaire was designed focusing on advantages and disadvantages of hadrontherapy, current status and possible future improvements, and need and opportunities for future investments in Italy and abroad. Information about professional qualifications, main fields of clinical involvement and specific competencies of the respondents was also collected.
The survey was completed by 121 AIFM members (response rate 12.2%). In the answers collected, it was shown that medical physicists expressed interest in hadrontherapy mainly for reasons of personal interest rather than for professional needs (90% ± 2.5% vs. 52% ± 4.3% of the respondents, respectively), with a good knowledge of the related basic aspects as well as of the pros and cons of its application. However, poor knowledge of the current status of hadrontherapy was observed among the medical physicists not directly involved at a professional level, who were less than 3% of the physicists working in radiotherapy.
In light of these results, the implementation of new training and education initiatives should be devised to promote a deeper and global knowledge of hadrontherapy-related issues, not only from a theoretical point of view but also in practical terms. Moreover, a close collaboration between highly specialized medical physicists employed in hadrontherapy centers and others in oncology hospitals should be encouraged.
Tumori 2017; 103(5): 430 - 437
Article Type: ORIGINAL RESEARCH ARTICLE
AuthorsTommaso Giandini, Chiara Tenconi, Mauro Carrara, Mario Ciocca, Stefania Russo, Costanza M.V. Panaino, Federica Cattani, Delia Ciardo, Sara Morlino, Barbara Avuzzi, Nice Bedini, Sergio Villa, Giulia Marvaso, Paola Romanelli, Azusa Hasegawa, Barbara Vischioni, Francesca Valvo, Barbara A. Jereczek-Fossa, Roberto Orecchia, Riccardo Valdagni, Emanuele Pignoli
- • Accepted on 26/05/2017
- • Available online on 08/07/2017
- • Published in print on 18/09/2017
This article is available as full text PDF.
Hadrontherapy (HT) is earning an increasingly important place in the era of modern external beam radiation therapy (RT). According to the Particle Therapy Co-operative Group (PTCOG), more than 50 HT centers are operating worldwide, with a growing number of facilities under construction or in the planning stages (1-2-3). The potential for a significant clinical gain related to the use of HT has clearly motivated a substantial and growing interest by the international scientific community, as reflected also by the increased number of publications on this topic (4). Lively debates are still ongoing regarding several issues: the expectation of some groups of researchers is that in the near future, a large fraction of definitive radiation treatments will be based on HT (5), while others call for caution until more robust clinical evidence will provide guarantees of survival and quality-of-life benefits in the long term (6). It is urgent nowadays to invest resources to identify the patients who would benefit most from HT and to determine the magnitude of those benefits (5). Several studies are being conducted, examining the use of HT in comparison with other RT modalities for several tumor sites, exploring radiobiological issues and investigating new technical solutions (7). Additionally, other factors such as cost-effectiveness, radiation safety aspects and increased training and staff needs, have been examined (8, 9).
In Italy, HT started in 2002 with low-energy protons at the Istituto Nazionale di Fisica Nucleare–Laboratori Nazionali del Sud, Catania (INFN-LNS Nuclear Physics Laboratory Catania) for the treatment of ocular pathology (10). Currently, 2 hospital-based facilities are in operation in the country: the Azienda Provinciale per i Servizi Sanitari (Proton Therapy Center, Hospital of Trento, APSS) in Trento, with proton-scanning beams, and the National Center for Oncological Hadrontherapy (CNAO) in Pavia, where treatments have been performed with both proton and carbon ion scanning beams since 2012.
Together with clinicians, biologists and biomedical engineers, medical physicists play a central role (i.e., in beam commissioning, quality control procedures, validation of complex dose calculation algorithms, particle beam dosimetry, verification and optimization of the treatments) in the rapidly developing field of HT (1).
The present survey was carried out to provide a snapshot of the point of view of medical physicists about the burgeoning field of HT, in the framework of a multi-institutional research project (IG-14300) supported by the Italian Associazione Italiana per la Ricerca sul Cancro (Association of Cancer Research; AIRC). A questionnaire was developed with the collaboration of the 3 oncology centers involved in the project – namely, the National Cancer Institute (INT) and the European Institute of Oncology (IEO), both located in Milan, and the CNAO – aiming at understanding the perceptions of Italian medical physicists regarding HT. An analogous survey was carried out among radiation oncologists in the Associazione Italiana Radioterapia Oncologica (Italian Association of Radiation Oncology; AIRO) (11).
Materials and methods
An e-mail requesting that the recipient fill out a digital copy of the questionnaire was sent during the last week of January 2016 to all active members of the AIFM with the association’s newsletter. By the same means, a few reminders were sent during the collection process. The anonymous responses of the participants were collected and administered through Web-based survey software (Google Forms) between the end of January and the beginning of April 2016.
In the introductory section of the questionnaire, the participants were asked about their professional qualifications, fields of clinical involvement (i.e., radiotherapy (RT), radiology, nuclear medicine, HT and/or radioprotection) and sources of information about HT. A question with several subitems about specific competencies in the HT field came next. All of these subitems had closed-ended responses using a 5-point scale. A numerical score from 1 to 5 (i.e., 1 = very poor; 2 = poor; 3 = moderate; 4 = good; 5 = very good) was defined for each subitem, and the average score (AS) with a cutoff of 3.5 was used to divide the participants into 2 subgroups according to their declared competence level in HT – i.e., expert (AS ≥3.5) or non-expert (AS <3.5). The main body of the questionnaire focused on 3 main topics: (i) subjective perceptions of the pros and cons of HT; (ii) current status of HT and possible further technical improvements; (iii) needs and opportunities for future investments in Italy and abroad. All of the questions asked (except the introductory section) are listed in
Questions in the main sections of the survey
|HT = hadrontherapy; IMRT = intensity-modulated radiation therapy; RT = radiation therapy; VMAT = Volumetric Modulated Arc Therapy.|
|Specific competencies in HT||1.
|1.1 Principles of beam production, acceleration and delivery systems|
|1.2 Beam interaction with matter, linear energy transfer (LET) and energy deposition|
|1.3 Radiobiology, relative biological effectiveness (RBE), oxygen enhancement ratio (OER)|
|1.4 Treatment planning system (TPS) and dose calculation models|
|1.5 Patient immobilization systems and target volume localization|
|2.1 At a professional level|
|2.2 For your personal background|
|Pros and cons of HT||
|4.1/5.1 Increased efficacy in treatment of radioresistant tumors|
|4.2/5.2 Reduction of toxicity to organs at risk and healthy tissues, due to a better conformability of the high doses to the target|
|4.3/5.3 Reduction of toxicity to organs at risk and healthy tissues due to a lower spreading of the medium/low doses|
|4.4/5.4 Increased efficacy in tumor hypoxic cells|
|4.5/5.5 Reduction of the dependence on the efficacy of the treatment on the cellular cycle|
|4.6/5.6 Reduction in the number of treatment fractions|
|6.1/7.1 Lack of robust clinical evidence|
|6.2/7.2 Uncertainties regarding dose calculation (approximations and biological issues)|
|6.3/7.3 Uncertainties independent of dose calculation (organ motion, particle range uncertainty in patient)|
|6.4/7.4 Too high start-up and maintenance costs of HT facilities|
|HT current status||8.
|8.1 External beam RT|
|8.3 Proton therapy|
|8.4 HT with carbon ions|
|8.5 HT with other particles (low/high LET such as 4He/16O)|
|9.2 Neutrons (BNCT)|
|9.3 Carbon ions|
|9.4 Low LET ions (4He)|
|9.5 High LET ions (16O)|
|Future prospects for HT||17.
|18.1 External beam RT|
|18.3 Proton therapy|
|18.4 HT with carbon ions|
|18.5 HT with other heavy particles|
|19.1 Only proton therapy|
|19.2 Only HT with carbon ions|
|19.3 Proton therapy and HT with carbon ions|
|19.4 HT with other heavy particles|
For the results for the surveyed items, frequencies and percentages of the questionnaire responses were reported. Assuming that the survey respondents were randomly distributed among the population of AIFM members, the sampling error (
where p is the number of positive answers among the n respondents, and N is the number of the overall population of AIFM members. For some items, comparisons were made between the overall collected responses and the ones given by the subgroups of experts and non-experts. A further stratification of the participants based on their years of working experience (with a cutoff of 5 years between senior and young) was also considered in the analysis. Statistical significance of the differences in the responses was analyzed with the unpaired Student’s t-test. Significant values were defined as those with a p value <0.05.
Characteristics of the respondents
A total of 121 responses were received out of the 991 e-mails sent to the AIFM members to solicit their participation in the survey, for a response rate of 12.2%. The characteristics of the respondents were as follows: 19% were trainees in medical physics, 20.7% were experts in medical physics for less than 5 years and 64.3% were experts in medical physics for more than 5 years (including 12 heads of medical physics units). For occupation (multiple choices allowed), 72.7% of respondents reported being involved in radiotherapy (RT) (including 9.9% of these involved directly in HT), 39.7% in radiology, 21.5% in nuclear medicine and 31.4% in radioprotection.
The specific competencies of the respondents with respect to different aspects related to HT were investigated, resulting in the competence levels provided in
Specific competencies of the respondents (N = 121)
|HT-related aspects||% (no.) of answers for each competence level|
|1 (very poor)||2 (poor)||3 (moderate)||4 (good)||5 (very good)|
|Principles of beam production and acceleration and delivery systems||1.7% (2)||19% (23)||40.5% (49)||30.6% (37)||8.3% (10)|
|Beam interaction with matter, linear energy transfer (LET) and energy deposition||0% (0)||7.4% (9)||41.3% (50)||36.4% (44)||14.9% (18)|
|Radiobiology, relative biological effectiveness (RBE), oxygen enhancement ratio (OER)||2.4% (3)||20.7% (25)||37.2% (45)||30.6% (37)||9.1% (11)|
|Treatment planning system (TPS) and dose calculation models||13.2% (16)||31.4% (38)||30.6% (37)||16.5% (20)||8.3% (10)|
|Patient immobilization systems and target volume localization||7.4% (9)||32.2% (39)||31.4% (38)||21.5% (26)||7.4% (9)|
47.9% ± 4.3% of respondents agreed that conferences are the main way to acquire specific knowledge about HT. The same result was confirmed for senior physicists. Among young physicists, 52.1% ± 4.3% also identified academic courses as a valuable source of information. Regarding educational needs in the HT field, most AIFM respondents (about 90%) reported that they were motivated more by personal interest than by the requirements of their professional activities (about 50%).
Advantages and disadvantages of HT
The potential reduction of toxicity to organs at risk and healthy tissues – firstly, due to a lower spreading of medium and low doses, and secondly, due to better conformability of high doses to the target – was perceived as the main advantage of proton therapy. This benefit was found to be statistically significant compared with other possible pros such as efficacy in the treatment of radioresistant tumors, radiobiological effectiveness (both in terms of efficacy with hypoxic cells and reduction of the dependence on the cellular cycle) and the reduction in the number of treatment fractions. With regard to the last 2 benefits, the number of participants who did not answer increased significantly to about 30% and 20%, respectively from about 6% for the other benefits. Similar results were found comparing the answers provided by experts and non-experts.
Efficacy in the treatment of radioresistant tumors and hypoxic cells was indicated as the key advantage of carbon ions (p<0.05). The same relevance was ascribed to a significant sparing of healthy tissues and also to the reduction of the dependence of the efficacy of the treatment on the cellular cycle. The reduction in the number of fractions was not perceived as an essential advantage. No relevant difference was found between the answers provided by experts and non-experts.
There was a consensus in considering the start-up and maintenance costs as the main disadvantages of HT. For protons, organ motion and particle range uncertainties in patients were considered another relevant weak point compared with the uncertainties of dose calculation (p<0.05), especially in the opinion of the experts.
For carbon ions, the same relevance was assigned to the lack of robust clinical evidence and to the uncertainties related to organ motion and particle range and dose calculation. In particular, experts highlighted the importance of organ motion and particle range uncertainties rather than the disadvantages of the lack of robust clinical evidence (p<0.05). Moreover, except for the lack of clinical evidence, experts considered all of the cons in the use of carbon ions to be more relevant (p<0.05) than non-experts did.
Current status of HT
HT is in general considered the technique with the greatest potential for improvement (p<0.05). In particular, 87.6% ± 2.8% of the AIFM respondents estimated that there is great development potential for proton therapy, 85.1% ± 3.0% asserted the same for treatment with carbon ions and 70.2% ± 3.9% believe that treatments with other heavier particles are likely to be improved substantially. Although the difference was not statistically significant, experts were in general more inclined to support the potential development of HT than non-experts.
Protons and carbon ions are considered the particles with the highest potential for the effective treatment of tumors (p<0.05). In contrast, more than 50% ± 4.3% of the AIFM respondents asserted that boron neutron capture therapy (BNCT) had the lowest treatment potential. Experts and non-experts were of the same opinion, even if
More than 80% ± 3.4% of the AIFM respondents agreed with the use of HT in treating cancers that respond poorly to conventional therapies. About half of them believe in the
In general, 37.2% ± 4.1% of the AIFM respondents believe that, to meet national needs, from 3 to 5 HT facilities would be necessary. The same result was confirmed by 50.0% ± 4.3% of experts, with the other 47.0% ± 4.3% equally split between those who demand up to 10 facilities and those who think that 2 facilities would be sufficient. The answers provided by non-experts were more heterogeneous, with a significant number of respondents (24.1%) who replied that they did not know.
To verify the level of knowledge of the survey participants regarding the current situation for worldwide HT, in the second part of this section in the survey, 6 questions were asked regarding the number of HT facilities currently operating in Italy, in Europe (Italy excluded) and worldwide (Europe excluded). The actual numbers were obtained from the website of the PTCOG (3) and are reported in parentheses in
Survey participants’ perceptions of the current status of hadrontherapy (HT). (
With the exception of the situation in Italy, statistically significant differences were found between the percentage of right answers provided by experts and non-experts for the number of proton therapy facilities in Europe and worldwide (experts 38.2% vs. non-experts 20.7%, and experts 61.8% vs. non-experts 17.2%, respectively) and for the number of facilities with carbon ions in Europe and worldwide (experts 72.5% vs. non-experts 52.9% and experts 50.0% vs. non-experts 29.9%, respectively). The low frequencies of right answers were due to a general trend of underestimation of the number of operating facilities.
Future perspectives regarding HT
About 75% ± 3.7% of the AIFM respondents think that substantial economic and scientific resources should be invested in proton therapy. External beam RT and HT with carbon ions are also considered treatment modalities deserving investment for about 70% ± 3.9% and 65% ± 4.1% of the AIFM respondents, respectively; whereas HT with heavier ions had a significantly lower rating for deserving investment (about 45% ± 4.2%). In contrast to non-experts, experts were more likely to stress the need for investments in HT, rather than in external beam RT (p<0.05).
Almost 40% ± 4.2% of the AIFM respondents had a correct idea about the resources that are actually being invested in the world for the design and building of new HT facilities – i.e., mainly proton therapy facilities (3). However, more than 30% ± 3.9% of the AIFM respondents declared they had no idea about the future prospects of HT.
As testified to by a large part of the literature, the debate within the scientific community regarding HT’s cost vs. benefits is still completely unresolved (4). Although HT is currently experiencing remarkable growth in Italy, as in the rest of the world, it started from a low level compared with other RT techniques (12). Known since 1946, its diffusion has been limited mainly due to the high costs for starting up and maintaining facilities. Moreover, external RT with photons has reached such a substantial level of sophistication, accuracy and safety that this may have contributed to a lack of urgency in the progress of HT. Nevertheless, in the recent past, the technological improvements and the clinical evidence for protons have become stronger, resulting in a steeper growth curve for proton facilities rather than for carbon ion facilities (13). For heavier particles, there is a longer road ahead, the biggest barrier being the cost-effectiveness justification for investments of huge magnitude (14).
In the past few decades, the contribution of medical physics to the evolving field of RT has been noteworthy. To respond to changes today, new efforts need to be undertaken particularly in those treatment modalities, such as HT, in which many countries are investing heavily in light of their potential effectiveness (6).
According to data from the AIFM, in Italy the number of medical physicists is currently about 1,000, mainly employed in the National Health Service, both in public and private hospitals variously distributed throughout the country. In particular, the main occupation field of the majority of the AIFM members is RT (69%), followed by radiodiagnostics (59%) (15). Among the physicists who are involved in RT, a small percentage (<3%) work in the HT centers active in the country.
The present study aimed to survey the opinions and knowledge about HT of medical physicists who are members of AIFM, while the views of radiation oncologists who are members of AIRO were simultaneously investigated by Marvaso et al, providing complementary and valuable insights into this topic (11). In particular, 32.24% and 32.42% of radiation oncologists who responded to that survey admitted average knowledge about the rationale for HT radiobiology and ongoing particle therapy clinical trials, respectively. Radioresistant tumors are perceived by 39.3% of the AIRO 224 respondents to be principal indications for carbon ions, while 37% consider pediatric malignancies as principal indications for proton therapy. Moreover, reirradiation is highly recommended by more than 50% of the radiation oncologists, and 35.7% believe that from 3 to 5 HT facilities would be necessary in Italy.
Compared with that for Marvaso et al (11), a lower response rate was obtained in our survey, (12.2 % vs about 20%) with the daily number of responses reaching maximum values exactly in conjunction with the reminders sent by means of the AIFM newsletter. A possible reason for the lower response rate could be that medical physicists not operating in the HT field were inherently less motivated to participate in answering the questionnaire than the few who are directly involved. In fact, the survey showed that 90 ± 2.5% of the AIFM respondents are interested in HT mainly for reasons of personal interest rather than for professional needs (52% ± 4.3%). If, on the one hand, this result was to be expected due to the small number of physicists working directly in, or collaborating with, HT facilities, on the other hand, it highlights the fact that AIFM respondents consider HT as an important topic for their cultural background. In any case, the number of responses was statistically significant to fulfill the objective of the survey, which was to outline the perceptions and expectations of AIFM members about HT, and to identify their current knowledge.
This survey showed that the pros and cons related to radiobiological aspects of HT appear to be generally less clear to the members of AIFM than those related to physical and technical aspects. The survey participants with a good knowledge in HT rationally stressed the importance of uncertainties related to organ motion or particle range, because of their potentially strong influence on treatment accuracy (16). However, even if the awareness of professionals of HT’s current limitations was high, experts generally supported the potential of this treatment modality because of its advantages in terms of superior achievable dose distributions and biological efficacy (13).
Our investigation showed that there is a shortage of information about the current worldwide status of HT and that, in general, the respondents underestimate the actual number of operating facilities in the world. For non-experts in this field, the estimation of the national need is also not obvious, while the majority of the survey participants had correct perceptions about the worldwide investments in proton therapy for the future (3) and about the negative cost to benefits balance of investments in heavier ions, even in the long run. On the other side, 30% ± 3.9% of the AIFM respondents declaring they have no idea about the future prospects of HT is a quite disappointing result from this survey. It highlights the fact that, except for professionals who are directly involved, the current and future situations of HT seem not to create widespread interest among AIFM members.
The results obtained and related considerations might also become a starting point for further initiatives and training programs primarily to strengthen those offered on the national scene. A multitude of events, seminars, meetings and conferences are indeed organized by national and international associations to meet the compelling need for staff education and training for a safe and efficient application of modern RT techniques, HT included. According to the results of the survey, conferences provide the main opportunities to improve HT knowledge. Considering only young AIFM respondents, the data also suggest that education in HT in academic programs nowadays is more thorough compared with in the past. This highlights the fact that there are ongoing efforts to effectively meet educational needs and to fill the gaps in competencies in the most advanced and/or less widespread RT fields, which in the recent past, has been left to a small group of dedicated researchers. To better define optimal educational programs, it would be desirable also to reinforce exchanges and collaboration between institutions within the country and abroad (17).
This survey provided a snapshot of AIFM members’ views on HT. It showed that AIFM medical physicists express interest in HT mainly for reasons of personal interest, with a good knowledge of the related basic aspects, as well as of the pros and cons of its application. An overall confidence in the development potential of HT with protons and carbon ions was also expressed. Medical physicists who are not directly involved in HT at a professional level show a poor knowledge about the current situation of HT, but the majority are aware of the direction of future investments.
In light of the results of this survey, the implementation of new training and education initiatives should be devised to promote a deeper and more widespread knowledge of HT-related issues, not only from a theoretical point of view but also in practical terms, including cost to benefit evaluations, national and international needs and investment opportunities. Moreover, a close collaboration between highly specialized medical physicists employed in HT centers and those in other oncology hospitals is one of the key requirements to make the best use of the available and future resources and to guarantee significant improvements for cancer patients.
We thank the members of the Associazione Italiana di Fisica Medica (AIFM) who took part in the survey. The authors are very grateful to AIFM for its support and the permission to publish the data of the survey, and they would also like to express their gratitude to Enirco Sironi for his help with the statistical analysis.
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Medical Physics Unit, Department of Diagnostic Imaging and Radiotherapy, Fondazione IRCCS National Cancer Institute, Milan - Italy
Prostate Cancer Program, Fondazione IRCCS National Cancer Institute, Milan - Italy
Department of Radiotherapy, IEO European Institute of Oncology, Milan - Italy
Medical Physics Unit, Oncology Institute of Southern Switzerland, Bellinzona - Switzerland
Medical Physics Division, CNAO National Center of Oncological Hadrontherapy, Pavia - Italy
Cancer Research UK, Manchester Institute, University of Manchester, Manchester - UK
Department of Medical Physics, European Institute of Oncology, Milan - Italy
Radiation Oncology 1, Department of Diagnostic Imaging and Radiotherapy, Fondazione IRCCS National Cancer Institute, Milan - Italy
Clinical Division, CNAO National Center of Oncological Hadrontherapy, Pavia - Italy
Department of Oncology and Hemato-oncology, University of Milan, Milan - Italy
Scientific Direction, European Institute of Oncology, Milan - Italy