Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
I wish all success to your journal and look forward to sending you any suitable similar article in future"



Dr Mohan Z Mani,
Professor & Head,
Department of Dermatolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Reviews
Year : 2024 | Month : February | Volume : 18 | Issue : 2 | Page : XE01 - XE07 Full Version

Current Perspectives on Proton Therapy: Techniques Shaping the Future of Cancer Treatment


Published: February 1, 2024 | DOI: https://doi.org/10.7860/JCDR/2024/68692.18992
Tamalika Chakraborty, Ammar A Razzak Mahmood, Jyoti Kataria, Amutha Chellathurai, Vanitha Innocent Rani, Muthu Prasanna

1. Assistant Professor, Department of Life Science, Guru Nanak Institute of Pharmaceutical Science and Technology, Kolkata, West Bengal, India. 2. Professor, Department of Pharmaceutical Chemistry, College of Pharmacy, University of Baghdad, Bab-Al-Mouadam, Baghdad, Iraq. 3. Assistant Professor, Department of Physiotherapy, Banarsidas Chandiwala Institute of Physiotherapy, New Delhi, India. 4. Lecturer, Department of Nursing-paediatric, King Khalid University, Abha, Saudi Arabia. 5. Assistant Professor, Department of Nursing Psychiatric, King Khalid University, Abha, Saudi Arabia. 6. Professor, Department of Pharmaceutical Biotechnology, Surya School of Pharmacy, Villupuram, Tamil Nadu, India.

Correspondence Address :
Vanitha Innocent Rani,
Assistant Professor, Department of Nursing Psychiatric, King Khalid University, Abha, Saudi Arabia.
E-mail: muthuprasanna78@gmail.com

Abstract

Traditional Radiation Therapy (RT) predominantly comprises a targeted therapeutic strategy focused on improving localised tumour control and achieving a cure while minimising the occurrence of adverse side effects. It could be feasible to take advantage of the better dose distribution by enabling larger RT dosages to the malignancy while preventing a rise in the toxicity of RT-induced healthy tissue, or by reducing adverse reactions to manageable levels. Poor local disease control and important dose-limiting normal tissue, which prevent safe dosage increase with conventional photon RT, have been the key justifications for RT. Proton treatment, on the other hand, delivers therapeutic protons or positive particles using proton beams. The potential advantage of protons’ physical properties allows for more localised RT delivery. By increasing the dosage to equitoxic levels, it is also possible to take advantage of the potential improvement in normal tissue sparing to support local tumour management and, ideally, longevity. Proton treatment preserves more important structures than photon therapy because of its unique physics. Thus, there is a need for wide usage of Proton Therapy (PT) for successive cancer treatment. The present review focuses on PT based on tumour site, clinical studies, biological barriers, instrumentation of PT, significance, and limitations.

Keywords

Proton beams, Proton treatment, Radiation therapy, Tissue toxicity

The primary goal of Radiotherapy (RT) is to deliver an appropriate dose to a malignancy while causing the least amount of injury to adjacent natural tissues. Clinical evidence indicates a correlation between radiation dosage and positive outcomes in malignancies, with higher doses improving overall survival and local control rates (1). However, the challenge lies in balancing the benefits of increased doses with potential damage, especially when combined with chemotherapy. Conventional RT aims for targeted intervention, optimising dosage distribution for effective tumour control while minimising harm to healthy tissues.

Proton Therapy (PT), utilising therapeutic protons, offers advantages in localised delivery compared to conventional photon therapy. Since 2015, PT has expanded globally, initially focusing on uveal melanomas and cranial base tumours, and later extending to various other disease areas (2). Research into PT started in 2020 (3), with initial efforts in 2015 at the Lawrence Berkeley Laboratory. The partnership between Uppsala University, Harvard University, and Massachusetts General Hospital contributed to the clinical introduction of proton treatment (4). The rise in treatment facilities worldwide reflects a preference for PT due to its precision in delivering ionising radiation (5).

The PT aims to enhance dosage distribution, sparing normal tissues and potentially improving therapeutic outcomes. The preservation of healthy tissue is considered crucial in radiation oncology, even in the absence of extensive clinical evidence, according to proponents of Proton Beam Therapy (PBT). The assessment of PT’s potential benefits often relies on previously published clinical data, given the limited availability of prospective randomised outcome trials (6).

Patients are increasingly exploring proton radiation as an alternative for locally advanced malignancies, drawn to its unique physics that preserve critical anatomical structures more effectively than conventional photon therapy. Proton beams, with their distinctive physical properties, allow for conformal radiation dosages, strategically adjusting proton energies to preserve neighbouring healthy tissues (7). PT is particularly favoured when the primary goal is to safeguard crucial organs, as protons demonstrate heightened sensitivity to organ motion and anatomical changes compared to photons. The features of PT and conventional RT are tabulated in the following table (Table/Fig 1) (8),(9).

The primary distinction between protons and X-rays lies in the physical characteristics of the proton beam (10). PT directs a stream of proton particles specifically to the tumour, reducing the risk of harming surrounding healthy tissues. In contrast, conventional radiation uses X-rays or photon beams that can extend past the tumour, potentially damaging adjacent healthy tissues and leading to notable side effects. PT utilises the Bragg peak phenomenon to achieve precise dose distribution, safeguarding healthy tissue. It employs proton beams, which have low linear energy transfer, and the effective dose is calculated by multiplying the physical dosage by the Relative Biological Efficiency (RBE), which is influenced by tissue type, dosage, dose rate, energy, and penetration depth. Estimates suggest that the elevated RBE might reach 2.05 at the conclusion of the Bragg peak (11). The RBE of protons is expected to be 1.1, similar to photons. Understanding the molecular mechanisms behind PT for treating resistant cancer cells, particularly cancer stem cells, is limited. Ionisation, a process involving alteration of atomic properties, is the basis for the advantages of RT (12). Ionisation damages Deoxyribonucleic Acid (DNA), affecting cell activities like division and growth. Enzymes repair damage, but severe damage prevents repair. Cancer cells cannot repair molecular damage, causing longer-term harm and cell death. This allows harmful cells to develop alongside healthy ones, ultimately destroying healthy cells (13). Protons regulate energy release in the body, slowing down and interacting more frequently with electrons. The greatest energy release is experienced by the cancer volume. Compared to the cells in the defined volume, the surrounding healthy cells are substantially less damaged (14). Radiation oncologists can increase radiation dosage to tumour sites while minimising exposure to healthy tissues, enabling higher doses beyond lower conformity therapies, potentially reducing side effects, enhancing tumour impact, and improving management (15).

Instrumentation of PT

A proton beam for therapeutic purposes requires a source of protons accelerated to the required energy levels using hydrogen and an electrical field. Cyclotrons and synchrotrons are commonly used for proton acceleration, progressing in a spiraling motion, accumulating energy and allowing for the generation of protons with varying energy levels (16). Synchronous technology directs protons towards the gantry for tumour treatment, using various energy levels for precise beamline delivery.

Methods include 360-degree rotation gantry, inclined beam systems, and fixed beams for specific treatment angles (17). Protons are delivered to the patient using nozzles, which comprise several parts. There are two primary categorisations for proton delivery systems in the field of RT: passive beam scattering (scatterer) and dynamic spot scanning. The essential components integrated into the nozzle of a passive scatter system encompass scatter foils, a ridge filter or energy modulator wheel, an aperture, collimator, and a range compensator (Table/Fig 2). In this particular context, the objective is to irradiate the targeted tumour using high-energy ionising particles, specifically protons, which have been accelerated via a particle accelerator (18). Proton beams harm cells’ DNA, leading to cell death. Cancerous cells are more susceptible due to rapid division and reduced repair capacity. The Bragg peak, the depth-dose dispersion, represents the peak. Investigative studies have demonstrated that proton fields possess the capacity to decrease the radiation dose to nearby healthy tissues by roughly 50% in contrast to photon beams (19). Protons’ comparatively enormous mass prevents them from scattering much through tissue, keeping the beam narrowly concentrated on the tumour’s form without harming the tissue around it. No proton can go more than a set distance with all protons of a certain energy.

Patient Selection for PT

The PT treatment is most effective when it considers the risk of hazard and tumour control. PT facilities have limited space and high costs, making patient selection crucial. PT is essential for parietal tumours and brain tumours with radio-resistant malignancy, as protons carry more energy than X-rays. PT is recommended for head and neck malignancies, nasal cavity tumours, nasopharyngeal cancer, metastatic carcinomas, medulloblastoma, endocrinologically reactive adenoma, sarcoma, retroperitoneal sarcomas, endocrinologically reactive adenoma, sarcoma near vital organs, lung cancer (20). Laryngeal cancer responds well to low radiation doses, while hypopharyngeal cancer, which cannot be surgically removed, has worse survival and RT (21). Patients with local or early non-small cell lung cancer, lymph nodes overlapping with T7, and centrally located tumours near the brachial plexus should undergo PT (22). In liver cancer, any tumours larger than five cm if standard irradiation is unable to provide sufficient coverage or beyond the average hepatic threshold, as well as dome and central tumours larger than three cm, PT was a choice for allowing for maximal liver sparing and perhaps lower radiation damage (23). Thus, precision in identifying eligible cases remains paramount for leveraging the advantages of PT in oncological care.

PT on Different Tumour Sites

Randomised proton bombardment investigations primarily employ two distinct proton dosage levels subsequent to photon irradiation, and they corroborate the findings of photon trials, indicating that a higher dose is associated with enhanced disease control, albeit at the expense of heightened late gastrointestinal complications (24).

Treating patients with Central Nervous System (CNS) cancers presents a challenge in balancing morbidity and cure. PT is effective in reducing radiation exposure to critical structures like the orbit bone, reducing morbidity, and maintaining treatment efficacy in CNS cancer cases. It significantly reduces the mean dose to the temporal lobes, with the most pronounced sparing effect observed when using Intensity-modulated Proton Therapy (IMPT) with fine pencil beams (25). PT, particularly advanced techniques like IMPT, offers superior precision and targeted treatment, minimising radiation exposure to critical brain structures like the temporal lobes. It also safeguards healthy tissues, reducing exposure to radiation in organs like the thyroid, heart, oesophagus, liver, and gastrointestinal tract (26). PT’s precision in dosage distribution allows for targeted radiation delivery, reducing exposure to critical organs and tissues, reducing acute toxicities, and improving patient quality of life. It is expected to significantly impact oncology, potentially saving cancer survivors from late effects (27). By precisely targeting tumours while significantly limiting radiation to surrounding healthy tissues, PBT offers a promising prospect for cancer patients (28).

Tumours at the Skull Base and Brain

Chondromas and chordomas are common neoplasms near the skull’s base, with a more pronounced presence in the sacrum and cervical regions. Proton treatment primarily targets cranial tumours, leading to RT. However, evidence supporting RT’s superiority over surgery in managing chordomas and chondrosarcomas remains limited (29). RT is recommended for individuals presenting unresectable and residual tumours postsurgery due to the growing prevalence of such chordomas that are challenging to remove completely. The primary rationale for employing PT is to reduce radiation exposure to the brainstem, facilitating a safe increase in radiation dosage to the primary tumour. This escalation in radiation dose aims to enhance tumour control and overall survival. The most widely accepted measure for assessing the efficacy of surgical intervention and RT is the actuarial assessment of local tumour control, commonly referred to as local Progression Free Survival (local PFS). It compares Proton Beam Cancer Therapy (PBCT) and RT. PBCT employs a high-energy proton beam to precisely administer radiation to target tumours, contrasting with conventional RT, which utilises high-energy X-rays (30). PBCT is a newer form of RT that irradiates tumours with minimal impact on adjacent tissues, unlike RT, which can damage surrounding tissues. It is particularly effective for tumours near sensitive organs like the brain, spine, and eyes.

Tumours of Eye

Numerous therapeutic modalities, including but not limited to local excision, enucleation, transpupillary thermotherapy, photodynamic therapy, and the utilisation of brachytherapy techniques employing isotopes such as ruthenium-106 and iodine-125, alongside advanced treatments like stereotactic photon RT and PT, are accessible to individuals who have been diagnosed with uveal melanomas. The efficacy of these therapeutic interventions, with regard to achieving local tumour control and enhancing overall survival, exhibits a striking degree of comparability, especially among patients with early-stage tumours (31). Plaque brachytherapy is not a viable treatment option for tumours that extend near the optic disc or the fovea on their posterior edge, or for tumours with a height exceeding 5.5 mm, as it may lead to the development of optic neuropathy (32). Hence, proton RT has been recommended as an alternative. Photons in fractionated stereotactic RT have also been used to treat patients with ocular melanoma who were not candidates for plaque treatment. The outcomes are comparable to proton therapy, both in terms of local tumour reduction and morbidity (33).

Prostate Cancer

The RT, including modern photon methods like conformal, Intensity-modulated Radiation Therapy (IMRT), and brachytherapy, is effective in treating locally advanced prostate cancer, but no trials show protons’ use improves tumour control or survival. High-dose proton improvement in prostate cancer treatment may reduce disease recurrence, but RT may cause negative side-effects due to damage to healthy tissues. The primary manifestations frequently observed in individuals undergoing RT pertain to complications affecting the urinary and rectal systems (34). It is noteworthy that a majority of these issues are of a temporary nature, although there exist the potential for radiation-induced morbidity to endure over an extended duration. In the context of radiation treatment, it is imperative to restrict the administered radiation dose in order to minimise toxicity-related concerns. Consequently, the utilisation of PT offers a viable strategy to enhance the radiation dose delivered to tumours while preserving the integrity of adjacent tissues within their tolerance limits (35).

Tumours at Head and Neck

The PT effectively addresses head and neck malignancies, particularly skin, early-stage tonsil tumours, salivary gland tumours, and mouth and throat cancers, as it targets only one side of the head or neck (36). Since very little proximal dose sparing is required for those situations, the geometries of these targets often make such situations amenable to successful treatment using passive scattering approaches. The efficiency of PT due to its single-field optimisation permits reliable treatment planning and minimises risk in these head and neck cancers.

In these kinds of circumstances, proton dosimetry is perfect as it allows for significant organ sparing by eliminating the exit dose using PT (37). Intensity-modulated PT stands out for its efficacy in significant reduction of doses to these sensitive areas (38). Proton-based approaches offer significant dose reduction to multiple organs at risk, enhancing treatment outcomes and minimising side-effects for patients with carcinomas. This innovative treatment method reduces neurological and visual side-effects, improving patient outcomes and treatment tolerability. A study showed optimal dose-volume coverage improved results in patients with recurrence of nasopharyngeal carcinoma (39),(40). The present research highlighted that individuals having PT showed significantly better outcomes than those with conventional treatment, emphasising the critical role of dosage precision in PBT for recurrent cases of nasopharyngeal carcinoma. Research on PT dosimetry has demonstrated the superiority of PBT over photon-based treatment for oropharyngeal carcinoma (41). PT can serve as an effective modality for addressing the heterogeneous nature of head and neck malignancies. It is imperative to differentiate between primary areas of concern and those that do not warrant special attention. For instance, laryngeal cancer does not merit significant consideration since it routinely receives low-dose RT and typically exhibits a favourable prognosis. Conversely, hypopharyngeal cancer, which cannot be surgically excised and is often managed with radiation over larger target volumes, presents a markedly poorer prognosis (42). The utilisation of PT presents a potentially superior alternative to conventional chemotherapy due to the demand for higher curative doses, which often exceed what can presently be administered, while also taking into account the associated adverse effects (43). Surgical and RT are the primary treatments for localised head and neck cancer, with the prognosis varying based on the cancer’s stage and treatment response. Patients with favourable treatment tend to have a more optimistic prognosis (Table/Fig 3).

PT based on Tumour Site for Children

Children with cancer can benefit from proton treatment since it has a lower potential for damaging healthy, growing tissue (44). PT could offer advantages to children afflicted with malignancies affecting the eye and CNS, including conditions like retinoblastoma and orbital rhabdomyosarcoma (45). PT is a state-of-the-art radiation method that can significantly reduce the adverse effects of conventional RT for paediatric tumours. Customised to individual patient needs, it minimises long-term side-effects and maximises therapy effectiveness, especially in brain tumours (46). In paediatric cancers affecting the eyes, such as retinoblastoma, PT’s precision is vital in preserving vision. PT is a site-specific cancer treatment for children with rare sarcomas or spinal tumours, reducing damage to organs and tissues and improving overall survival rates to 80% over the past few decades (47). Despite numerous clinical trials aimed at reducing its impact, radiation continues to play a substantial role in the treatment of over half of paediatric patients. IMRT offers improved dose precision, yet it also presents a challenge by exposing a considerable amount of healthy tissues to low levels of radiation, potentially posing risks for younger patients (48).

Breast Cancer

The PT has emerged as an exciting RT modality for breast cancer due to the ability to minimise exposure to the heart, lungs, muscle, and bone. Breast cancer accounts for 30% of new cancer diagnosis in women. As the number of patients cured from breast cancer increases with improvements in multidisciplinary care, emphasis on reducing late therapeutic toxicity has increased to improve long-term quality of life (49). PT not only reduces non target normal tissue exposure but also may improve target coverage of difficult-to-treat areas such as the Internal Mammary Nodes (IMNs), which lie adjacent to the heart and lungs. Therefore, PBT represents a promising approach to improve long-term treatment outcomes. PT presents an exciting RT option for breast cancer by minimising heart, lung, muscle, and bone exposure. Constituting 30% of new cancer diagnosis in women, breast cancer’s rising cure rates emphasises the need to reduce treatment toxicity, enhancing long-term quality of life (50). PT’s potential to reduce non target tissue exposure and improve coverage in challenging areas like IMNs is promising for long-term treatment effectiveness. However, the risk of major coronary events increases with mean heart dose, emphasising the need to limit low-dose cardiac exposure (51). The Surveillance, Epidemiology, and End Results (SEER) study on breast cancer survivors found a rise in secondary malignancy risk due to factors like age, follow-up duration, and tissue irradiation. Proton PT could potentially minimise radiation exposure and mitigate long-term risks. A study suggests that PT may be more effective than photon therapy in treating left-sided breast cancer, potentially reducing cardiac-related complications and reducing the risk of recurrence by about 1% and 3%, respectively (52). Accelerated Partial Breast Irradiation (APBI) stands as a well-established adjunctive therapy subsequent to lumpectomy, particularly for women aged over 50 years, exhibiting favourable early-stage breast cancer characteristics such as absence of lymph node involvement and hormone receptor positivity. APBI combined with PBT highlights its efficacy in maintaining high rates of breast tumour control (53).

Clinical Studies of PT

Numerous clinical investigations have extensively analysed PT’s efficacy across various tumour sites, with each study typically involving a cohort of no fewer than 20 patients and a follow-up period of atleast two years (54). Critical research areas include head and neck tumours (55),(56), with two studies covering 62 patients, revealing valuable insights into PT’s application for these conditions. Additionally, studies focusing on prostate cancer (involving 1,642 patients) (57),(58), ocular tumours (encompassing 1,406 patients) (59), gastrointestinal cancer (involving 76 patients) (60),(61), lung cancer (with 125 patients) (62),(63),(64), and CNS tumours (encompassing 146 patients) (65),(66) have significantly contributed to understanding PT’s impact across these specific cancers. Furthermore, investigations into sarcomas (with 47 patients) (67), and studies exploring PT’s potential for less common tumour sites (61 patients) (68),(69) further enrich the diverse body of evidence supporting its utility. Overall, this collective research, involving studies with 3,565 patients, greatly enhances comprehension of PT’s effectiveness, aiming to refine treatment options and improve outcomes for oncology patients across various cancer types. These studies were tabulated in the following (Table/Fig 4) (55),(56),(57),(58),(59),(60),(61),(62),(63),(64),(65),(66),(67),(68),(69).

Significance of PT in Clinical Oncology

Current clinical evidence indicates that PT is atleast as proficient as photon techniques in disease control, and there is a growing body of evidence suggesting reduced toxicities associated with proton treatments. PT exhibits dosimetric superiority compared to photon therapy by better preserving normal tissue, especially at lower to moderate dose levels. This capability enables the delivery of increased tumouricidal doses. Proton treatment minimises harm to surrounding healthy tissues while accurately targeting malignancies. Malignancies close to vulnerable or vital organs benefit greatly from this precision. In comparison with standard RT, its focused nature lowers the likelihood of long-term problems and adverse reactions, therefore being appropriate for juvenile patients and less damaging to normal tissues. PT may result in fewer side effects both during and following treatment, improving the quality of life by protecting healthy tissues. Since proton beams focus most of their energy on the tumour, they may target it with a greater radiation dosage while exposing fewer adjacent healthy tissues to radiation. For certain malignancies, including those in children, tumours near vital organs, malignancies in the brain, and tumours in the eyes, proton treatment is very beneficial. Even with the significant installation expenses at first, proton treatment could eventually prove to be more affordable due to the possibility of fewer problems and shorter long-term healthcare requirements. Utilising PT requires tumours near critical structures and robust evidence supporting increased radiation dosage for improved tumour control and survival. Growing interest exists in tumour treatment via PT to minimise healthy tissue exposure (70).

Limitation(s)

While PT offers superior dose precision compared to photons, several unanswered queries persist. These include identifying the patient demographics that benefit most from PT, assessing whether proton dose escalation enhances curative outcomes for a broader range of patients, understanding how PT reduces treatment-related toxicities to improve patients’ quality of life, exploring the potential for shorter treatment durations, and determining the synergies between PT and other modalities like surgery, chemotherapy, and photon therapy (70). Protons may be cost-effective for certain tumour groups, but evidence is lacking for superior treatment outcomes compared to photon therapy. Higher costs of PT, primarily due to extended facility hours, are a critical limitation for this therapy (71). PT offers fewer severe side effects, but questions remain about patient demographics, treatment schedule feasibility, and collaboration potential. Challenges include the complexity of proton acceleration equipment.

Conclusion

The PT, though technologically advanced, lacks substantial clinical evidence in demonstrating clear survival or toxicity benefits compared to standard radiation treatments. Despite its potential in reducing normal tissue toxicity and allowing dose escalation for improved disease control, the absence of peer-reviewed data showing its superiority remains a critical concern. The proliferation of PT units seems commercially driven, lacking emphasis on evidence-based medicine. However, this absence of proof shouldn’t dismiss the technology but should incite well-structured trials focused on clinically relevant endpoints. Identification of suitable tumour targets and prospective studies devoid of commercial influences are crucial for validating the theoretical benefits of PT, particularly in cancers near critical organs like lung, oesophageal, and hepatocellular cancers, ensuring improved outcomes with tangible clinical evidence.

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DOI and Others

DOI: 10.7860/JCDR/2024/68692.18992

Date of Submission: Nov 23, 2023
Date of Peer Review: Dec 12, 2023
Date of Acceptance: Dec 29, 2023
Date of Publishing: Feb 01, 2024

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was informed consent obtained from the subjects involved in the study? NA
• For any images presented appropriate consent has been obtained from the subjects. NA

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Nov 25, 2023
• Manual Googling: Dec 23, 2023
• iThenticate Software: Dec 26, 2023 (9%)

ETYMOLOGY: Author Origin

EMENDATIONS: 7

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