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Abstract

Cancer continues to be a significant health challenge despite advancements in our understanding of its development and treatment methods. Managing cancer in clinical settings remains highly complex. Currently, healthcare providers employ various treatment modalities, including surgery, chemotherapy, radiation therapy, immunotherapy, and hormone therapy. Recent improvements in radiotherapy technology have greatly enhanced cancer treatment outcomes by providing better tumor control, increasing survival rates, and improving the quality of life for patients. Current research in beam radiation therapy primarily focuses on enhancing techniques such as External Beam Radiation Therapy (EBRT), Intensity-Modulated Radiation Therapy (IMRT), and Proton Therapy to achieve more precise tumor targeting while minimizing damage to adjacent healthy tissues. Additionally, internal radiation therapies like brachytherapy, along with innovative methods such as Stereotactic Body Radiation Therapy (SBRT) and FLASH radiotherapy (FLASH-RT), are gaining traction due to their potential benefits for challenging cancers. Radiation therapy remains a crucial component of cancer treatment; approximately half of all cancer patients will receive radiation at some stage of their care, contributing significantly to curing about 40% of cancers. The fundamental principle behind radiation therapy is straightforward yet vital: it functions by damaging the DNA within cancer cells, inhibiting their ability to grow or replicate. This review aims to examine how radiation therapy operates, its application in contemporary medicine, and the exciting developments aimed at further enhancing its effectiveness.

Keywords

Beam Radiation Therapy, Cancer Treatment, Radiotherapy, External Beam Radiation Therapy (EBRT), Oncology, Tumor Control

Introduction

Radiation therapy—commonly referred to as radiotherapy—is a prevalent and effective method for treating cancer. It utilizes high-energy beams to target and eliminate cancerous cells. The most frequently employed method involves X-rays; however, newer alternatives like proton therapy are also emerging. Often abbreviated as RT, this form of treatment can be administered alone or in conjunction with other therapies like surgery or chemotherapy. While highly effective at combating cancer, radiation therapy does carry certain risks; it can inadvertently affect surrounding healthy tissues and organs leading to severe side effects or lasting damage. Particularly challenging cases include advanced cancers such as glioblastoma brain tumors and pancreatic or lung cancers that often show poor responsiveness to treatments with low survival rates. Fortunately, technological advances have rendered radiation therapy more precise and effective over time. These innovations enable physicians to better target tumors which can lead to improved patient outcomes and higher survival probabilities.

Radiation may be administered through different methods depending on the source's location:

  1. External Beam Radiation Therapy (EBRT): This is the most common approach where radiation is generated from outside the body.
  2. Internal Radiation Therapy (also known as brachytherapy): Involves placing a small radioactive source near or inside the tumor.
  3. Systemic Radioisotope Therapy: Involves administering radioactive substances orally or via injection that circulate throughout the body targeting cancer cells. The choice among these types depends on various factors including cancer type and location with an objective towards destroying malignant cells while safeguarding healthy ones wherever possible.

Type

1. External Beam Radiation Therapy (EBRT):

It is widely recognized as the primary form of radiation treatment for cancer. It directs high-energy beams—typically X-rays but occasionally electrons or protons at tumors using machines positioned externally from the patient's body.

Figure 1: External beam radiation therapy

 Several advanced variants of EBRT exist that are specifically designed to enhance precision:-

  • 3D Conformal Radiation Therapy (3D-CRT) : Utilizes CT imaging combined with specialized software that constructs a three dimensional representation of the tumor allowing tailored shaping of radiation beams according to its size and shape thereby limiting exposure of nearby healthy areas.
  • Intensity-Modulated Radiation Therapy (IMRT): An advanced iteration of 3D-CRT utilizing multiple variable-intensity beams which enables higher doses directed at tumors while reducing exposure risk for surrounding tissues.
  • Stereotactic Body Radiation Therapy (SBRT): Similar in concept to SRS but applied for tumors located outside the brain such as those found in lungs or liver delivering concentrated doses over fewer sessions
  • Intraoperative Radiation Therapy (IORT): Administered during surgical procedures post-tumor excision directly targets any residual malignant cells within an area.

2. Internal Radiation Therapy:

Internal radiation therapy entails positioning a radioactive substance close to the tumor site within the body itself commonly utilized for cancers affecting head/neck regions breast cervix uterus or prostate areas:

Figure 2: Internal beam radiation therapy

  • Brachytherapy: Involves inserting tiny radioactive devices dubbed "seeds" either directly into or near tumors releasing focused radiation aimed at eradicating malignancies some being temporary while others remain permanently but diminish their radioactivity over time
  • Systemic Radiation Therapy: Administers liquid radioisotopes either orally or intravenously allowing them to circulate through bloodstreams targeting widespread cancers where they may exist; a variant called radio immunotherapy employs radioactive proteins specifically designed for targeting malignant cells attaching themselves delivering localized irradiation directly.

Advancement and Technologies Currently Used:

  • Particle Therapy Proton and heavy ion therapies: provide refined delivery mechanisms differing from conventional X-rays harnessing a phenomenon known as Bragg peak providing maximal dose precisely where required while minimizing extraneous exposure particularly beneficial near delicate organs.
  • Volumetric Modulated Arc Therapy (VMAT): An evolution in IMRT VMAT incorporates continuous arc delivery around patients adjusting both beam shape intensity dynamically ensuring swift efficient accurate treatment execution.
  • FLASH Radiotherapy: Currently under investigation FLASH delivers high doses rapidly within fractions enabling lower collateral damage potentially enhancing immune responses against malignancies exhibiting promising early findings.
  • Adaptive Radiotherapy: This technique permits real-time adjustments throughout treatments accommodating changes resulting from tumor shrinkage/body anatomical variations maintaining accuracy effectiveness duly addressed during ongoing  therapies.
  • Image-Guided Radiation Therapy (IGRT): Employs real-time imaging technologies such as CT/PET scans per session enabling practitioners’ precise localization adjustments accounting shifts since prior administrations fostering enhanced alignment minimizing potential hazards associated with non-target exposure leading thus towards smaller safety margins overall reduced harm inflicted upon healthy structures involved therein.

Table 1: Advantages and disadvantages for radiation therapies

Sr No.

Beam radiation therapy technologies

Types of cancer treated

Advantages

Disadvantages

1.

3 dimensional conformal radiotherapy (3DCRT)

Brain tumors, breast , gastrointestinal (GI) cancer, lung cancer and gynecologic malignancies

Improve short-term response rate, reduce mouth dryness and parotid gland injury, and promote the prognosis of patients with nasopharyngeal carcinoma.

Shows higher GI toxicities in patients with endometrial cancers. Difficult to perform correct quality procedures, positioning, imaging, contouring, dosimetry, follow-up, and dose delivery

2.

Intensity modulated radiotherapy (IMRT

Head and neck, prostate, breast, lung, brain, gynecologic, and GI cancers.

Provides high conformity and high precision.

IMRT is prone to geometrical errors, due to higher dose conformity indices.

3.

Volumetric modulated arc therapy (VMAT)

Head and neck, non-small cell lung cancer (NSCLC), prostate, gastrointestinal, gynecological, thoracic, central nervous system, and breast tumors

Provides a full 360° of beam directions with the entire dose volume delivered in a single rotation VMAT treatment shows a lower risk of OAR irradiation and has better homogeneity compared to IMRT. Significant role in uncomfortable immobilization.

Increase in the low dose radiation to the surrounding tissues and organs, with a greater chance of having secondary malignancies.

4.

Image guided radiotherapy (IGRT)

Prostate, lung and head and neck cancers

Significant reduction in set-up margins resulting in reduced toxicities in sites with demonstrable, quantifiable, and correctable inter/ or intra- fraction motion

Uncertainties in target volume delineation, image quality, longer acquisition times, high intra-fractional errors, and extra-dose delivery during daily imaging

5.

Stereotactic body radiation therapy (SBRT)

Prostate, head and neck, spinal, renal,metastases, and pancreatic

Provides high doses of radiation to the tumor and has low risk of postoperative risk and death.

Post treatment side-effects.

6.

Particle therapy Proton Neutron Carbon

Stage II–III NSCLC, prostate carcinoma, and hepatocellular carcinoma etc.

Particle radiation has a higher biological effectiveness and is very effective in radio-resistant cancers.

The production of particle radiation therapy is much more expensive than the production of photons, and has more logistical requirements

Challenges And Future Prospects 

Current Challenges:

  1. Side Effects Risk: Protecting normal tissues/organs adjacent tumours emerges critical given potential side effects adversely impacting patient wellness/contentment levels.
  2. Resistance Issues: Certain malignancies exhibit diminished responsiveness towards radiations necessitating combinatorial approaches integrating chemotherapies/ immunotherapies alongside traditional modalities boosting recovery prospects .
  3. Access  Disparity: Globally many individuals especially residing underprivileged states lack requisite access hindering standard care availability intensifying poorer survival statistics reflected therein .
  4. Complex Processes: High resource demands/ precision requisites persist notably concerning intricate cases even employing latest modalities calling forth substantial expertise across disciplines involved .
  5. Infrastructure Deficiencies: Scarcities regarding centers/ machineries/ proficient personnel hinder comprehensive quality provision especially witnessed remote regions underserved previously discusse.

Future Prospects:

1. Advanced Treatment Approaches :

  • Nanotechnology leveraging minute particles enhances tumour sensitivity bolstering targeted therapeutic efficacy promoting immune responses concurrently activated therein .
  • Proton/Ion Therapeutics offer controlled methodologies minimizing tissue harm though remaining exorbitant technologically sophisticated necessitating scaled adaptations across practices .

2. Combinatorial Strategies For Enhanced Outcomes :

  • Immunotherapeutics synergizing alongside radiative measures bolster immune recognition facilitating heightened attack ratios against neoplastic growths increasingly becoming prevalent investigations .
  • Targeted therapeutics based upon individual biological markers permit personalized regimentations augmenting success probability concomitantly mitigating adverse reactions experienced overall .

Objectives:

  1. Achieving Optimal Therapeutic Ratio :

Striking balance between adequate destruction versus preservation ratios deemed essential ensuring maximizing efficacy whilst safeguarding integrity surrounding cellular constituents encountered therein .

  1. Reducing Adverse Effects :

Minimizing collateral damages critical fostering comfortable recoveries thereby improving life quality experienced ultimately benefitting long-term well-being observed through consistent evaluations conducted periodically thereafter .

  1. Enhancing Survival Rates/Welfare Levels :

Modernized interventions aspire not solely eradicate neoplasias aiming simultaneously uplift longevity improving patient lifestyles amidst therapeutic diversifications adopted accordingly henceforth progressing steadily forward .

  1. Preserving Organ Functions :

Innovative techniques evolving protect critical organ functionalities vital preserving essential capabilities such speech/breathing bladder control resonates positively effectuating significant lifestyle enhancements .

  1. Dose Fractionation Techniques Smart Timings :

Segmental administration distributes cumulative dosages permitting reparatory intermissions aiding recovery whilst compounding cumulative detrimental accrual amongst neoplastic entities facilitating optimal therapeutic potentials realized fully evident thereafter .

CONCLUSION

Concluding insights reveal profound implications inherent beam-radiation applications facilitates impactful survivorship experiences alongside elevated living standards attributable ongoing evolutions witnessed current methodologies emphasizing intensity-modulated strategies coupled stereotactic interventions achieving remarkable efficiency targets preserving adjacent non-cancerous environments concurrently alleviating toxicity concerns faced historically previously exhibited thus underscoring persistent challenges existing particularly addressing resistive formations demanding attention moving forth conclusively directing expansive future inquiries dedicated amalgamative explorations aimed refining holistic therapeutic trajectories advancing patient welfare progressively hence forthwith noted consequently reaffirmed herein.

REFERENCES

    1. Baskar R, Lee KA, Yeo R, Yeoh KW. Cancer and Radiation Therapy: current Advances and Future Directions. Int J Med Sci. 2012;9(3):193–199. Doi: 10.7150/ijms.3635 [DOI] [PMC free article] [PubMed] [Google Scholar]
    2. Orth M, Lauber K, Niyazi M, et al. Current concepts in clinical radiation oncology. Radiate Environ Biopsy’s. 2014;53(1):1–29. Doi: 10.1007/s00411-013-0497 [DOI] [PMC free article] [PubMed]
    3. National Cancer Institute. External Beam Radiation Therapy for Cancer. (https://www.cancer.gov/about cancer/treatment/types/radiation-therapy/external-beam) Accessed 9/7/2022.
    4. Cleveland Clinic: Radiation Therapy for Cancer (https://my.clevelandclinic.org/health/treatments/17637-radiation-therapy)
    5. Chargari, C., Deutsch, E., Blanchard, P., et al. (2019). Brachytherapy: An overview for clinicians. CA: A Cancer Journal for Clinicians, 69(5), 386–401. https://doi.org/10.3322/caac.21561
    6. Haberkorn, U., Kratochwil, C., & Giesel, F. (2020). Internal radiation therapy. In Recent Results in Cancer Research (Vol. 216, pp. 881–902). https://doi.org/10.1007/978-3-030-29045-2_31
    7. Maani, E. V., & Maani, C. V. (2021, October 26). Radiation therapy. In StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK537036/
    8. National Cancer Institute. (n.d.). External beam radiation therapy for cancer. https://www.cancer.gov/about-cancer/treatment/types/radiation-therapy/external-beam
    9. Voshart, D. C., Wiedemann, J., van Luijk, P., & Barazzuol, L. (2021). Regional responses in radiation-induced normal tissue damage. Cancers (Basel), 13(3), 367. https://doi.org/10.3390/cancers13030367.
    10. Mohan, G., T P, A.H., A J, J. et al. Recent advances in radiotherapy and its associated side effects in cancer—a review. JoBAZ 80, 14 (2019). https://doi.org/10.1186/s41936-019-0083-5
    11. Begg, A. C., Stewart, F. A., & Vens, C. (2011). Strategies to improve radiotherapy with targeted drugs. Nature Reviews. Cancer, 11(4), 239–253.
    12. Benveniste, M. F. K., Welsh, J., Godoy, M. C. B., Betancourt, S. L., Mawlawi, O. R., & Munden, R. F. (2013). New era of radiotherapy: An update in radiation-induced lung disease. Clinical Radiology, 68(6), e275–e290. https://doi.org/10.1016/j.crad.2013.01.013.
    13. Bujold, A., Craig, T., Jaffray, D., & Dawson, L. A. (2012). Image-guided radiotherapy: Has it influenced patient outcomes?. Seminars in radiation oncology. WB Saunders 22, 1, 50–61p. https://doi.org/10.1016/j.semradonc.2011.09.001.
    14. Cozzi, L., Dinshaw, K. A., Shrivastava, S. K., Mahantshetty, U., Engineer, R., Deshpande, D. D., … Fogliata, A. (2008). A treatment planning study comparing volumetric arc modulation with RapidArc and fixed field IMRT for cervix uteri radiotherapy. Radiotherapy and Oncology, 89(2), 180–191.
    15. Baskar R, Lee KA, Yeo R, Yeoh KW. Cancer and Radiation Therapy: current Advances and Future Directions. Int J Med Sci. 2012;9(3):193–199. doi:10.7150/ijms.3635.
    16. Orth M, Lauber K, Niyazi M, et al. Current concepts in clinical radiation oncology. Radiat Environ Biophys. 2014;53(1):1–29. doi:10.1007/s00411 013-0497-2.
    17. Barnett GC, West CML, Dunning AM, et al. Normal tissue reactions to radiotherapy. Nat Rev Cancer. 2009;9(2):134–142. doi:10.1038/nrc258.
    18. Prasanna PGS, Stone HB, Wong RS, et al. Normal tissue protection for improving radiotherapy: where are the Gaps? Transl Cancer Res. 2012;1(1). doi:10.21037/372.
    19. Lee TF, Yang J, Huang EY, Lee CC, Chan MF, Liu A. Technical Advancement of Radiation Therapy. Biomed Res Int. 2014;2014:e797412. doi:10.1155/2014/797412.
    20. Garibaldi C, Jereczek-Fossa BA, Marvaso G, et al. Recent advances in radiation oncology. Ecancermedicalscience. 2017;11:785. doi:10.3332/ ecancer.2017.785
    21. Tseng M, Ho F, Leong YH, et al. Emerging radiotherapy technologies and trends in nasopharyngeal cancer. Cancer Commun. 2020;40(9):395–405. doi:10.1002/cac2.12082
    22. Shirato H, Le QT, Kobashi K, et al. Selection of external beam radiotherapy approaches for precise and accurate cancer treatment. J Radiat Res. 2018;59(Suppl 1):i2–i10. doi:10.1093/jrr/rrx092.

Reference

  1. Baskar R, Lee KA, Yeo R, Yeoh KW. Cancer and Radiation Therapy: current Advances and Future Directions. Int J Med Sci. 2012;9(3):193–199. Doi: 10.7150/ijms.3635 [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Orth M, Lauber K, Niyazi M, et al. Current concepts in clinical radiation oncology. Radiate Environ Biopsy’s. 2014;53(1):1–29. Doi: 10.1007/s00411-013-0497 [DOI] [PMC free article] [PubMed]
  3. National Cancer Institute. External Beam Radiation Therapy for Cancer. (https://www.cancer.gov/about cancer/treatment/types/radiation-therapy/external-beam) Accessed 9/7/2022.
  4. Cleveland Clinic: Radiation Therapy for Cancer (https://my.clevelandclinic.org/health/treatments/17637-radiation-therapy)
  5. Chargari, C., Deutsch, E., Blanchard, P., et al. (2019). Brachytherapy: An overview for clinicians. CA: A Cancer Journal for Clinicians, 69(5), 386–401. https://doi.org/10.3322/caac.21561
  6. Haberkorn, U., Kratochwil, C., & Giesel, F. (2020). Internal radiation therapy. In Recent Results in Cancer Research (Vol. 216, pp. 881–902). https://doi.org/10.1007/978-3-030-29045-2_31
  7. Maani, E. V., & Maani, C. V. (2021, October 26). Radiation therapy. In StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK537036/
  8. National Cancer Institute. (n.d.). External beam radiation therapy for cancer. https://www.cancer.gov/about-cancer/treatment/types/radiation-therapy/external-beam
  9. Voshart, D. C., Wiedemann, J., van Luijk, P., & Barazzuol, L. (2021). Regional responses in radiation-induced normal tissue damage. Cancers (Basel), 13(3), 367. https://doi.org/10.3390/cancers13030367.
  10. Mohan, G., T P, A.H., A J, J. et al. Recent advances in radiotherapy and its associated side effects in cancer—a review. JoBAZ 80, 14 (2019). https://doi.org/10.1186/s41936-019-0083-5
  11. Begg, A. C., Stewart, F. A., & Vens, C. (2011). Strategies to improve radiotherapy with targeted drugs. Nature Reviews. Cancer, 11(4), 239–253.
  12. Benveniste, M. F. K., Welsh, J., Godoy, M. C. B., Betancourt, S. L., Mawlawi, O. R., & Munden, R. F. (2013). New era of radiotherapy: An update in radiation-induced lung disease. Clinical Radiology, 68(6), e275–e290. https://doi.org/10.1016/j.crad.2013.01.013.
  13. Bujold, A., Craig, T., Jaffray, D., & Dawson, L. A. (2012). Image-guided radiotherapy: Has it influenced patient outcomes?. Seminars in radiation oncology. WB Saunders 22, 1, 50–61p. https://doi.org/10.1016/j.semradonc.2011.09.001.
  14. Cozzi, L., Dinshaw, K. A., Shrivastava, S. K., Mahantshetty, U., Engineer, R., Deshpande, D. D., … Fogliata, A. (2008). A treatment planning study comparing volumetric arc modulation with RapidArc and fixed field IMRT for cervix uteri radiotherapy. Radiotherapy and Oncology, 89(2), 180–191.
  15. Baskar R, Lee KA, Yeo R, Yeoh KW. Cancer and Radiation Therapy: current Advances and Future Directions. Int J Med Sci. 2012;9(3):193–199. doi:10.7150/ijms.3635.
  16. Orth M, Lauber K, Niyazi M, et al. Current concepts in clinical radiation oncology. Radiat Environ Biophys. 2014;53(1):1–29. doi:10.1007/s00411 013-0497-2.
  17. Barnett GC, West CML, Dunning AM, et al. Normal tissue reactions to radiotherapy. Nat Rev Cancer. 2009;9(2):134–142. doi:10.1038/nrc258.
  18. Prasanna PGS, Stone HB, Wong RS, et al. Normal tissue protection for improving radiotherapy: where are the Gaps? Transl Cancer Res. 2012;1(1). doi:10.21037/372.
  19. Lee TF, Yang J, Huang EY, Lee CC, Chan MF, Liu A. Technical Advancement of Radiation Therapy. Biomed Res Int. 2014;2014:e797412. doi:10.1155/2014/797412.
  20. Garibaldi C, Jereczek-Fossa BA, Marvaso G, et al. Recent advances in radiation oncology. Ecancermedicalscience. 2017;11:785. doi:10.3332/ ecancer.2017.785
  21. Tseng M, Ho F, Leong YH, et al. Emerging radiotherapy technologies and trends in nasopharyngeal cancer. Cancer Commun. 2020;40(9):395–405. doi:10.1002/cac2.12082
  22. Shirato H, Le QT, Kobashi K, et al. Selection of external beam radiotherapy approaches for precise and accurate cancer treatment. J Radiat Res. 2018;59(Suppl 1):i2–i10. doi:10.1093/jrr/rrx092.

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Pratiksha Pawar
Corresponding author

Department of pharmacy, Genba Sopanrao Moze College of Pharmacy, Wagholi, Pune

Photo
Tanvi Raskar
Co-author

Genba Sopanrao Moze College of Pharmacy, Wagholi, Pune

Photo
Sushma Nakhate
Co-author

Genba Sopanrao Moze College of Pharmacy, Wagholi, Pune

Photo
Dr. Tushar Shelke
Co-author

Genba Sopanrao Moze College of Pharmacy, Wagholi, Pune

Photo
Dr. Tushar Shelke
Co-author

Genba Sopanrao Moze College of Pharmacy, Wagholi, Pune

Pratiksha Pawar, Tanvi Raskar, Sushma Nakhate, Dr. Tushar Shelke, Beam Radiation Therapy for Cancer Treatment: Advancements and New Approaches, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 10, 285-292. https://doi.org/10.5281/zenodo.17255329

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