Radiation therapy is the treatment approach that depends entirely upon the utility of high energy rays and radioactive substances for damaging the tumoral cells and inhibiting their growth and division. It has shown efficacy in treating the early‐stage tumors involving different types of tumor as radical, organ‐sparing treatment. It is also used to cure locally advanced cancer alone or in combination with systemic therapies. It can also be used while being administered postoperatively for increasing the control over local disease and preoperatively for allowing less extensive surgery with better functional outcomes. Radiation therapy effectively relieves cancer-causing symptoms in the case of advanced or metastatic cancer types.
There are two significant types of radiation therapy involving electromagnetic and particulate ones. The advances in radiation therapy have enabled the delivery of more effective radiation doses for eliminating the tumor, which shows physical association to radiosensitive, essential organs and structures. Different types of radiation therapy are integrated into cancer treatment. The increased use of combined multimodality approaches, including radiotherapy and chemotherapy, has effectively treated locally advanced cancers. The technological advancement of radiation therapy in cancer treatment has been capable of confirming the high‐dose volume accurately concerning the tumor shape in an easy, faster and accessible manner. Although radiation therapy has shown drastic improvement in the reduction of toxicity in radiation therapy, many patients still have experienced adverse side-effects of radiation therapy during their treatment.
The side effects are observed during or within weeks after the completion of radiation therapy. Hence, screening and management for the radiation therapy side-effects are needed for better survivorship care among cancer patients and survivors.
Cancer is the principal global, and primary health issue which has affected a large population as 18 million cancer cases are diagnosed, and 9.6 million deaths have been estimated across the globe every year. The importance of multidisciplinary cancer has shown better results in providing the best cancer care to the patients, which was initiated in the early nineties. Multidisciplinary cancer teams are considered a vital cancer care intervention (Borras et al., 2015).
Radiation therapy is the treatment approach that depends entirely upon the utility of high energy rays and radioactive substances for damaging the tumoral cells and inhibiting their growth and division. It is used alone or in combination with other different types, showing efficacy in treating cancer for many years. In today’s modern era, radiation therapy is considered an important therapeutic tool for treating various types of cancer. Almost two-thirds of cancer patients receive radiation therapy in the form of unique treatment or as a part of the more complex therapeutic protocol. It is considered a critical curative treatment approach for uncomplicated locoregional tumors.
Radiation therapy has been considered a significant component of cancer care when combined with other treatment approaches such as surgery and systemic therapies. Almost more than half of cancer patients in their cancer journey undergo at least one radiation treatment, either alone or with other treatment methods. Radiation therapy has shown efficacy in treating the early‐stage tumors involving different types of tumor as radical, organ‐sparing treatment. It is also used to cure locally advanced cancer alone or in combination with systemic therapies. It can also be used while being administered postoperatively for increasing the control over local disease and preoperatively for allowing less extensive surgery with better functional outcomes. Radiation therapy effectively relieves cancer-causing symptoms in the case of advanced or metastatic cancer types.
Integrating new technologies has contributed to profiling protein expression and the immune system. The information regarding the tumor cells showing high variabilities in individual patients is achieved through this technological advancement. Radiation oncologists use these types of data to develop novel radiation sensitivity markers that will show efficacy in treatment. Radiation therapy alters the specific and systemic antitumor immune responses in metastatic cancer (Frey et al., 2014). Hence, the radiation oncologists utilize the advancement in radiation therapy in different domains involving the radiosensitivity markers such as reactive oxygen species (ROS), DNA repair, tumor microenvironment, and innovative strategies that integrate cancer genomics/epigenetics and immunology for implementing effective treatment for various metastatic cancer types.
The historical approach to Radiation Therapy:
The use of medicines was integrated for treating diseases that are malignant and benign. This era changed after the discovery of X-rays in 1895. The physical properties of x-rays were studied and explored. Later on, the physiologic effects of radium rays were also studied and researched. More studies were conducted using x-rays and radium in medicine. A device was developed capable of emitting higher energy X-rays to treat various cancer types. Most studies did not show the mechanism of action and appropriate knowledge of radiotherapy, so its efficacy in cancer treatment was not explored. The physicians estimated more information on the side effects.
Considering this, more studies were conducted depicting the information on the radioactive isotopes, type of rays and radiation techniques. This helped in a better understanding of the nature of radiations, their modalities of actions and the relationship between time and dose of radiations on cell survival. The effectiveness of the administration of the total radiation dose in fractionated ones and singular treatment sessions helped in controlling the adverse impact of cancer. With the advancement of technologies, more advanced devices were developed to treat cancer. Innovative devices with computerized control were introduced that helped improve cancer patients’ survival rates.
The use of iron beams was discovered to be considered the ideal tool in cancer therapy but showed difficulty in treating benign diseases. The introduction of the computerized 3D conformal radiotherapeutic device (Stereotactic radiation therapy) made the cancer treatment more accessible and more approachable, providing safety to the patients. Another advanced technological approach introduced adaptive radiation therapy, known as the particular form of image-guided radiotherapy (IGRT) optimized the treatment technique during radiotherapy with clinical relevance (Schwartz et al., 2012).
Types of radiation in radiation therapy:
There are two significant types of radiation therapy involving electromagnetic and particulate ones. Electromagnetic radiations affect the x-rays and gamma-rays; the other includes electrons, neutrons and protons. Radiation delivery in radiation therapy is carried out either externally or internally. The external radiation is achieved by delivering a beam of radiation through a source of radiation, which is external to the body. The internal radiations are delivered by placing a radioactive source inside the lesions, which is treated. Hence, the treatment choice in the radiation therapy depends on the localization, size and type of cancer.
Mechanism of delivery of radiations in radiation therapy:
The radiation therapy shows efficacy by killing the tumor cells and inhibiting their ability to produce more cells (Veness et al., 2012). This action of radiation damages the DNA or other critical cellular molecules due to the mechanism of particulate radiation, such as alpha particles, protons or electrons. It causes indirect cellular damage observed after producing free radicals such as x-rays or gamma-rays. The radiation therapy also involves dividing normal cells, which may be damaged or killed. The radiation beams are focussed on the tumor, and the total irradiation dose is fractionated so normal tissue can recover and repair itself (Ying, 2001).
Types of radiation therapy techniques
Technological advancements have led to improving the integration of existing and novel forms of computed tomography, magnetic resonance imaging, and positron emission tomography for describing the tumor condition among cancer patients. The integration of adaptive radiotherapy is achieved by technological advancement with the information about tumor processing and contouring of healthy tissue, along with integrating appropriate treatment planning. These advances in radiation therapy have enabled the delivery of more effective radiation doses for eliminating the tumor, which shows physical association to radiosensitive, essential organs and structures.
Following are the types of radiation therapy being integrated into cancer treatment.
- External beam radiation therapy: It is the standard type of radiation therapy in which the patients who are undergoing treatment has to lay down on a couch, and an external source of ionizing radiation, either photons, electrons, or particles, is pointed towards the specific region of the body
- Internal beam radiation therapy or Brachytherapy: It is the type of radiation therapy in which a sealed radiation source is used and placed next to or even inside the region of a patient’s body that requires treatment.
- Proton therapy: It is the type of external beam radiotherapy which utilizes a beam of the proton.
- Adaptive radiation therapy: It refers to the changes in the radiation treatment plan delivered to a patient during the time of radiation therapy that accounts for changes in the anatomy.
- Intraoperative radiation therapy (IORT) involves delivering a high dose of ionizing radiation towards a tumor located in a specific body part at the time of surgery.
- Spatially fractionated radiation therapy: It is the type of radiation therapy which is different from standard radiation approaches while treating an entire tumor with a non-uniform dose that stays within standard tissue tolerance of the surrounding structures.
- Stereotactic radiation therapy: It is the type of external beam radiation therapy that involves the treatment of tumor with high accuracy using high doses of radiation.
- Volumetric modulated arc radiotherapy (VMAT): It is the type of radiation therapy responsible for delivering the radiation dose in continuous mode as the treatment machine rotates. It gives accuracy to the radiation dose to the tumor while reducing the dose to the organs surrounding it.
- Image-guided radiation therapy (IGRT): It is the type of radiation therapy that uses imaging during radiation therapy to improve the precision and accuracy of treatment delivery.
- Flash radiation therapy: It is the type of radiation therapy that is different from standard radiation and uses ultra‐fast delivery of radiation treatment at dose rates having various orders of magnitude greater than those currently used in routine clinical practice.
The improvement in the imaging and radiation therapy includes the delivery of ablative doses during the early stage of cancer and delivery of standard radiation dose schedule in case of locally advanced tumors. The positive result is achieved by integrating radiation therapy in cancer treatment by increasing the space between the tumor and the organs at risk.
Radiation therapy in cancer treatment
The death rates due to cancer have reduced in some high-income countries as the overall level and treatment approaches have progressed (Bertuccio et al., 2019). Variations in the availability and access to screening programs and high‐quality cancer care have been observed in the treatment approach for various cancer types (Arnold et a;., 2019). Improved survival rates among cancer patients and improvement in surgical techniques have been observed after implementing advanced procedures. The increased use of combined multimodality approaches, including radiotherapy and chemotherapy, has effectively treated locally advanced cancers. When talking about distant‐stage cancers, improvements in survival rates have been one of the positive outcomes of cancer. Hence, the integration of radiation therapy has provided high-quality care to cancer patients while integrating individual, optimal treatment strategies.
The technological advancement of radiation therapy in cancer treatment has been capable of confirming the high‐dose volume accurately concerning the tumor shape in an easy, faster and accessible manner. The efficacy and safety of radiation therapy are improved by enhancing the biological knowledge in clinical treatment schedules (Krause et al., 2020). Radiation therapy has shown efficacy in curing many cancer patients while improving their chances of prolonged survival, even for some patients with a history of non-curable cancer. Apart from providing a prolonged survival rate to cancer patients, radiation therapy has been capable of improving the well‐being of patients by providing relief from the symptoms and maintaining the functions of the body organs. The introduction of immunotherapy has changed the prognosis of cancer patients with advanced stages, providing more chances of long-term survival (Yu et al., 2019).
Although progress has been made in radiation therapy that contributed to cancer care, still there is a requirement for improving the quality and accessibility of care for patients with early and advanced‐stage cancer. Drug delivery administration is considered empirical in cancer treatment, but still, there is a need to integrate personalized treatment approaches for cancer that need clinical relevance. Hence, radiation therapy is a personalized treatment approach that has shown efficacy with better health outcomes among cancer patients.
Side-effects of radiation therapy
Around 40% of cancer patients have received at least one course of radiation therapy treatment (Lalani et al., 2017). It is used with both the treatment approaches such as curative and palliative care, showing efficacy in treating early-stage or locally advanced tumours, which is considered curative and managing symptoms in a progressive disease known as palliative. Although radiation therapy has shown drastic improvement in the reduction of toxicity in radiation therapy, many patients still have experienced adverse side-effects of radiation therapy during their treatment. The side effects are observed during or within weeks after the completion of radiation therapy. The side effects caused by radiation therapy are either localized or locoregional, which develop within tissues and organs that have been irradiated. The side effects produced during or within weeks after the completion of radiation therapy are known as early side effects. In contrast, the ones that occur months and years after radiation therapy treatment are known as late side effects (Bentzen, 2006).
The radiation oncologist, along with general practitioners and primary care providers, contributes to survivorship care, mainly involving the management of radiation therapy-induced side effects. The most common side effects observed among the patients undergoing radiation therapy involve anxiety, depression, and fatigue. The common side effects are discussed below:
- Distress, anxiety and depression: The increasing incidence of distress, anxiety and depression among the patients undergoing radiation therapy has been observed. Patients have been observed with decreasing symptoms of distress, anxiety, and depression after the completion of radiation therapy, but in several cases, the development of psychological effects after the treatment is expected (Stiegelis et al., 2004). Around 10%-20% of the patients suffer from depression and anxiety regardless of undergoing appropriate diagnosis and treatment (Kawase et al., 2012). Hence, to reduce the adverse effects of psychological issues, the patients should undergo screening tests for distress during their initial post-treatment visit and regular intervals after that, using validated tools. The conduction of nonpharmacological and pharmacological interventions is recommended for patients suffering from depression (Li et al., 2016).
- Fatigue: It is known as one of the most adverse impacts of radiation therapy. Approximately 80% of the patients suffer from acute fatigue after undergoing radiation therapy, and 30% suffer from chronic fatigue after undergoing radiation therapy (Turriziani et al., 2005). Hence, such patients are recommended to undergo screening in all cancer patients and take immediate action towards contributing factors such as anaemia, pain, and cardiac or endocrine dysfunction.
Therefore, it is revealed that radiation-induced side effects adversely impact the patient’s mental health, which deteriorates their quality of life. Hence, screening and management for the radiation therapy side-effects are needed for better survivorship care among cancer patients and survivors. Family physicians and general practitioners in oncology are the key drivers in managing comorbid conditions, promoting healthy lifestyles, and treating radiation-induced side effects.
- Borras JM, Lievens Y, Dunscombe P, Coffey M, Malicki J, Corral J, Gasparotto C, Defourny N, Barton M, Verhoeven R et al (2015) The optimal utilization proportion of external beam radiotherapy in European countries: an ESTRO‐HERO analysis. Radiother Oncol 116, 38–44.
- Frey B, Rubner Y, Kulzer L, Werthmoller N, Weiss EM, Fietkau R, Gaipl US. Antitumor immune responses induced by ionizing irradiation and further immune stimulation. Cancer Immunol Immunother: CII. 2014;63:29–36.
- Schwartz DL, et al. Adaptive radiotherapy for head-and-neck cancer:initial clinical outcomes from a prospective trial. Int. J. Radiat. Oncol. Biol. Phys. 2012;83:986–993. https://doi.org/10.1016/j.ijrobp.2011.08.017
- Veness M, Richards S. Radiotherapy. In: Bolognia J, Jorizzo J, Schaffer J, editors. Dermatology. Vol. 2. Philadelphia: WB Sauders; 2012. pp. 2291–2301.
- Ying CH. Update of Radiotherapy for Skin Cancer. Hong Kong Dermatology & Venereology Bulletin. 2001;9(2):52–58.
- Bertuccio P, Alicandro G, Malvezzi M, Carioli G, Boffetta P, Levi F, La Vecchia C and Negri E (2019) Cancer mortality in Europe in 2015 and an overview of trends since 1990. Ann Oncol 30, 1356–1369.
- Arnold M, Rutherford MJ, Bardot A, Ferlay J, Andersson TM, Myklebust TÅ, Tervonen H, Thursfield V, Ransom D, Shack L et al (2019) Progress in cancer survival, mortality, and incidence in seven high‐income countries 1995–2014 (ICBP SURVMARK‐2): a population‐based study. Lancet Oncol 20, 1493–1505.
- Krause M, Alsner J, Linge A, Bütof R, Löck S and Bristow R (2020) Specific requirements for translation of biological research into clinical radiation oncology. Mol Oncol 14, 1569–1576.
- Yu Y, Zeng D, Ou Q, Liu S, Li A, Chen Y, Lin D, Gao Q, Zhou H, Liao W et al (2019) Association of survival and immune‐related biomarkers with immunotherapy in patients with non‐small cell lung cancer: a meta‐analysis and individual patient‐level analysis. JAMA Netw Open 2, e196879.
- Lalani N, Cummings B, Halperin R, et al. The practice of radiation oncology in Canada. Int J Radiat Oncol Biol Phys. 2017;97:876–80. doi: 10.1016/j.ijrobp.2016.11.055.
- Bentzen SM. Preventing or reducing late side effects of radiation therapy: radiobiology meets molecular pathology. Nat Rev Cancer. 2006;6:702–13. doi: 10.1038/nrc1950.
- Stiegelis HE, Ranchor AV, Sanderman R. Psychological functioning in cancer patients treated with radiotherapy. Patient Educ Couns. 2004;52:131–41. doi: 10.1016/S0738-3991(03)00021-1.
- Kawase E, Karasawa K, Shimotsu S, et al. Estimation of anxiety and depression in patients with early stage breast cancer before and after radiation therapy. Breast Cancer. 2012;19:147–52. doi: 10.1007/s12282-010-0220-y.
- Li M, Kennedy EB, Byrne N, et al. Management of depression in patients with cancer: a clinical practice guideline. J Oncol Pract. 2016;12:747–56. doi: 10.1200/JOP.2016.011072.
Turriziani A, Mattiucci GC, Montoro C, et al. Radiotherapy-related fatigue: incidence and predictive factors. Rays. 2005;30:197–203.