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Radiation Dosimetry Biology And Protection

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Question:

Discuss About The Radiation Dosimetry Biology And Protection?

 

Answer:

Introduction

Radiation therapy, together with chemotherapy and surgery, is one of the most superior weapons of modern medicine that is being used for the treatment of cancer. Radiation therapy is administered externally with the help of a high-energy X-ray beams, or in an internal manner with the help of radioactive substances placed near the tumor being treated When such therapy is considered for both palliative and curative purposes, literature indicates that more than half of the total number of cancer patients need radiotherapy for at least once during their care (Greenwalt et al., 2016). According to Agrawal (2014), radiation therapy is considered as a pivotal component of comprehensive breast cancer treatment. Over the past one decade, conservation treatment for breast cancer has been in focus, and the application of post-mastectomy radiation has expanded rapidly, leading to increasing of the number of patients receiving post-operative irradiation. Synchronized modifications in the delivery of radiation therapy have been witnessed in the past; however, the technique has been much debated for its harmful impact on the patient. A patient being exposed to ionising radiation has been established to be a risk factor for several health complications. Research is going on across the world to understand the exact negative impact that radiation therapy has on breast cancer patients so that contemporary techniques can be developed and adopted (Offersen et al.,2017).

The present paper is a literature review on the risks associated with radiation therapy in breast cancer patient. It aims to analyse the existing literature on the concerned topic and highlight the gaps in the literature. The purpose is to understand the direction of future research that would bring a drastic change in the delivery of radiation therapy for breast cancer patients.

 

Literature review

Advancements in the screening and treatment of breast cancer have emerged from the research domain putting in efforts to enable best possible patient outcomes. The survival rate of breast cancer patients has increased solely due to such advancements, one of which is radiation therapy. For particular at-risk groups of women undergoing mastectomy for tumour removal, postmastectomy radiation therapy (PMRT) is known to reduce the risk of recurrence at the locoregion and improve chances of survival. Evidence-based studies and population-based studies point out to the fact that the use of radiation therapy is increasing with each passing year (Jethwa et al., 2017). However, studies on the impact of the radiation on the patient body post-therapy have thrown light on a number of risk factors associated with radiation exposure and are to be discussed in here.

Agrawal (2014) highlighted the concerns raised about the risk of chronic and acute side effects of radiation therapy in breast cancer survivors. As per the author, the most noteworthy impact of radiation therapy includes reproductive dysfunction, cardiac toxicity, skin changes, arm lymph oedema, pneumonitis (RP) and neuropathy. These are some of the complications arising from adjuvant treatment. Cardiovascular toxicity that is chemotherapy-induced include cardiomyopathy that might or might not be accompanied by endothelial dysfunction, overt congestive heart failure (CHF) and arrhythmias. RT-induced cardiovascular toxicity includes valvular disease, coronary artery disease (CAD), arrhythmias and conduction disturbances, chronic pericardial disease, carotid artery stenosis and cardiomyopathy. Reproductive dysfunction after radiation therapy is subjected to the age of the patient and the ovarian function when treatment is being done. Since the radiation cause depletion of follicle pool in a dose-and drug-dependent manner, the ovarian damage is evident. Apart from the negative impact of cancer therapy on ovarian function, much of the substantiation from literature strongly indicates a negative effect on bone. Cancer treatment-induced bone loss (CTIBL) is identified in a major proportion of patients becoming permanently or temporarily amenorrheic after therapy. As per the author, radiation pneumonitis in irradiated breast cancer patients is discussed in the literature for the last two decades.

The findings of Agrawal (2014) is supported by Cheng et al., (2017) who reported that radiotherapy of breast cancer involves incidental exposure of the heart to the harmful impact of ionising radiation. As per the authors, the impact of the exposure on risk of heart disease was uncertain. This uncertainty had been reported by a number of researchers previously and Cheng et al. attempted to judge the truthfulness of this matter. The researchers carried out a literature search with the help of MEDLINE and EMBASE databases with no particular restrictions. Meta-analysis was done for this purpose that indicated that radiation therapy had a strong association ith absolute risk increase of coronary heart disease (76.4 out of 100000 person-years and cardiac death (125.5 out of 100000 person-years). The risk had the tendency to increase within the first decade after radiation therapy for coronary heart disease and from the second decade of radiation therapy for cardiac mortality. Risks for such diseases were more in patients undergoing left-sided radiation therapy as compared to right-sided. The study inferred that though contemporary radiation therapy might reduce the risk rate, the chances of cardiotoxicity cannot be eliminated. The comparison of left-sided breast and right-sided breast cancer treatment with radiation therapy dates back to early 2000s. Giordano et al., (2005) had stated that patients with left-sided breast tumours are subjected to a higher dose of radiation to the heart than patients with right-sided tumours.

 


Jagsi (2013) pointed out that radiation therapy is a crucial element of the multidisciplinary management approach for invasive breast cancer. Radiation therapy not only brings improvement in local control of tissue growth but also spares the patients from the distress of recurrence. As per the authors, considerable progress is continuously being moving toward the widespread benefits of the therapy. Nevertheless, the toxicity concerns of therapy are to be brought into the limelight. The researchers highlighted that cardio-toxicity impacts of radiotherapy for breast cancer. When a patient is exposed to high radiation dose, exposure of the heart is a concern. Recent studies are noteworthy in raising concerns about modern, conformal techniques. The left anterior descending coronary artery is incidentally irradiated when high doses of radiation are give in tangential fields. Also, internal mammary lymph node when treated can result in exposure of the right coronary vessels to the radiation dose. While some studies have given the suggestion that cardiac risk magnitude has decreased recently, it is striking that perfusion defects are found in patients undergoing treatment with modern methods.

The similarity in findings is cited in the research of Darby et al., (2013) who carried out a population-based case-control study of major coronary events in 2168 patient undergoing radiation therapy after diagnosis of breast cancer. The coronary events included coronary revascularisation, myocardial infarction and death from heart disease. The primary result of the study was that exposure of the patient’s heart to radiation considerably leads to an increase in the rate of ischemic heart disease. The sharp increase has a direct proportionality with the dose of radiation and changes occur within a few years after first radiation exposure. It thereafter continues for as long as 20 years. Women who have preexisting cardiac risk factors suffer more risk from radiotherapy when compared to other women.

Research of Hong et al., (2017) however contradicted the studies of Agrawal, Darby and Cheng while they researched on the health outcomes of breast cancer radiation therapy based on the existing information that adjuvant radiation therapy (RT) for breat cancer leads to substantive cardiac dose and cardiac risk. The researchers attempted to assess the mean heart dose (MHD) of RT along with the estimated risk of cardiac toxicity in patients with breast cancer in a community practice. Bivariate analyses and multivariable linear regression tests were done with 1161 patients with left-sided breast cancer and receiving RT. The study concluded that MHD was in varying degrees across the set of patients and the technique of delivery influenced MHD in community settings. The overall risk of cardiac toxicity was unassertive. The findings are in alignment with the studies of Hauqe et al., (2011) whose research pointed out that radiation therapy had no direct association with cardiovascular disease when follow up was done for 14 years. The study also brought into focus that tumor laterality has the potential of modifying the association between radiation a cardiovascular disease.

The rationale for decreased risk of heart disease due to radiation therapy can be explained by the work of Giordano et al., (2005). The findings of the researchers had concluded that a considerable progress has been made in treatment planning for radiation therapy from the 1970s through late 2000s. The utilisation of large fraction sizes, orthovoltage radiation and deep tangential fields or direct anterior internal mammary fields for the treatment purpose techniques that were common in the early 2000s were a concern of risk of heart disease. However, the mentioned techniques are now not in use as standard practice. Another reason for decreased risk for heart disease can be attributed to the decreased use of an en face photon or cobalt 60 fields for treating the internal mammary lymph nodes and medial chest wall.

 


The impact of breast cancer radiotherapy on the risk of primary lung cancer has been well discussed in the literature. Kaufman et al., (2008) studied the impact radiation therapy and cigarette smoking has on the patient pertaining to second primary lung cancer. Prior studies had indicated that women with breast cancer are at increased risk of suffering from complciations from postmastectomy radiation therapy (PMRT) such as brachial plexopathy, lymphedema, pneumonitis and cardiac complications in later stages of life. Further, radiation was also found to be the cause of second primary cancer. The researchers had previously conducted studies that indicated that secondary lung cancer in a patient with breast cancer was more in frequency in the lung lying ipsilateral to the breast undergoing radiation in comparison to the contralateral lung. The risk associated has a latency period of least ten years. Further, smoking is a common risk factor for cancer in the lungs. Based on such previous research the researchers undertook a study to evaluate the risk of lung cancer due to PMRT among women who were smokers and non-smokers. A population-based nested case-control study was conducted with women participants wherein patient cases had lung cancer after ten years of diagnosis of breast cancer. Medical records underwent reviewing for therapy for breast cancer, pathology, and history of smoking. Among the total number of 113-second primary lung cancer patients, women who were non-smokers and receiving PMRT showed no higher risk of developing lung cancer when the comparison was done with women who were non-smokers and were not given PMRT. The study inferred that smoking, as well as PMRT, had a strong association with increased risk of lung cancer.

The study of Taylor et al., (2017) further contributes to the topic of discussion, that is a relationship between radiotherapy and lung cancer. The group of researchers estimated the absolute risks of advanced and modern breast cancer  radiotherapy that is for long-term. The background of this study was the knowledge that radiotherapy can lead to second cancer of lungs or heart diseases after a decade, as cited by Kaufman et al., (2008). Taylor and co-researchers conducted their research in three parts. First, the researchers carried out a systematic literature review of heart and lung doses in regimens for breast cancer published between the years 2010 and 2015. Thereafter, a meta-analysis was done with patient data wherein 40,781 women randomly assigned to breast cancer radiotherapy. Lastly, heart and lung Excess Rate Ratio (ERR) in the trials were combined to be applied to present cardiac mortality and lung cancer rates in data from a population with consideration of smoking and non-smoking. Estimated absolute risks relevant to modern radiotherapy were identified as: lung cancer, 0.3% for non-smokers and 4% for longterm smokers; and cardiac mortality, 0.3% for nonsmokers and 1% for smokers. It was therefore concluded that for patients who are long-term smokers, risks of radiotherapy have the potential to outweigh the multiple benefits of the therapy. For patients who do not smoke, the net impact of radiotherapy is more powerful. It is implied that smoking cessation has the ability to reduce the arising risks of radiotherapy in breast cancer patients.

The findings are consistent with the findings of the study by Grantzau and Overgaard (2015). As radiotherapy has been long linked with increased second cancer risk at sites of exposure, the researchers estimated the chances of suffering second-non-breast cancer after the patient underwent radiotherapy for breast cancer. The study was a meta-analysis that with the databases CINAHL and EMBASE. Primary endpoints were second cancers of oesophagus, lung, thyroid as well as second sarcomas. After a span of five years of radiotherapy, there was a statistically significant relationship with second non-breast cancer relative risk (RR), second lung cancer RR, oesophagus RR and second sarcomas RR. The risk also was found to be increasing with the passage of time, and the highest was reported at fifteen years of diagnosis of breast cancer for second oesophagus and lung cancer. There was no statistically significant association between second thyroid cancer and radiotherapy. The study proves that radiotherapy increases the chances of second non-breast cancer in organs adjacent to the treatment fields considered for therapy previously.

In this context, the work of Tunio et al., (2017) is to be cited. The group of researchers tried to answer the question that whether the thyroid gland is at risk in patients suffering breast cancer and undergoing locoregional supraclavicular radiotherapy. They presented the results of a pilot study. The aim of the study was the evaluation of the dose distribution within the thyroid gland and its relation with hypothyroidism in patients with breast cancer receiving supraclavicular radiation therapy. Forty patients having normal thyroid function tests were randomly assigned into two groups; supraclavicularradiation therapy and normal radiation therapy. From the study, it was indicated that risk of hypothyroidism in breast cancer patients after supraclavicular radiation therapy is dependent on the volume of the thyroid gland. Further, there is a chance of minimising the risk through shielding the thyroid gland.

Zeidan et al., (2017) analysed the risk of myeloid neoplasms in older women after undergoing radiotherapy with localised breast cancer. There has been an inconsistency in the data present on the risk of myeloid neoplasms (MN) among patients who have survived breast cancer after receiving radiotherapy. Surveillance, Epidemiology, and End Results (SEER)±Medicare linked database was used by the researchers for studying older women with breast cancer diagnosis and surgery. Radiation therapy was ascertained, and a new diagnosis of MN was recorded with the SEER registry. Out of the total 60426 patients, 316 women were found to be diagnosed with MN. The results had consistency with multiple sensitivity analyses. The data suggested that radiation therapy increases chances of MN among older cancer survivors. However, the risk is relatively small.

On assessing the risk factors for breast cancer recurrence after intraoperative radiation therapy (IORT), Sperk et al., (2017) had commented that lymphangioinvasion, young age, triple negative tumours, medial tumour localization and the resection status were confirmed as risk factors after IORT. Positive lymph nodes without lymphangioinvasion and size of the tumor were not noteworthy risk factors. High-risk factors were a combination of positive lymph nodes and lymphangioinvasion as well as triple negative tumors. Eldredge-Hindyet al., (2014) identified that breast IORT has a discreet toxicity profile that is marked by several changes in the body such as seroma formation, liponecrosis, fibrotic changes and calcifications. Studies have however indicated that skin toxicities lie dryness, hyperpigmentation, skin erythema and pruritus is mild and less frequent in patients with IORT. The researchers also noted that patients of breast cancer are undergoing radiation therapy experience complications apart from infection. This condition is marked by the deposit of brown fluid in the tumor bed with mild, overlying skin erythema. Fat necrosis commonly occurs in the body after one month of surgery in older women who have high amount of fat tissue in their breasts. Additionally, other studies document toxicity findings of radiation therapy. There is a certain heterogeneity in the reported rate of different toxicities in the literature. The dissimilarity is due to differences in IORT dose and techniques, nonuiform systems for toxicity scoring and varying follow-up length. Further, recall bias is also reported in retrospective series.

Kaidar-Person et al., (2015) criticised previous literature that showed that significantly fewer ipsilateral breast tumor recurrences are linked with the inclusion of whole-breast radiotherapy in the treatment plan with adjuvant endocrine therapy after surgery for breast cancer. The researchers recommended that as treatment with neither radiation therapy or endocrine therapy would lead to a detectable survival advantage, patients are to be aware of the high burden of complications arising from both the treatment. The complications that the therapies entail are to be analysed thoroughly for understanding the benefits and challenges. The study of Norman et al., (2010) contradicts the findings of studies highlighting the link between radiation therapy and impact on lymph by stating that that radiation therapy does not increase the risk of lymphedema. Though the study suggested the presence of other therapies as an influencing factor for risk due to radiation therapy, there is a need for more research into this matter for clarifying the arising doubts since different studies have considered different definitions for lymphedema.

 

Conclusion

Radiation therapy is being widely used across settings as the best possible treatment option for breast cancer. It provides a considerable reduction in regional and local recurrence rates for breast cancers in both early stage and locally advanced stage and contributes to progress in overall survival. A rich pool of data has attempted to assess the relationship between radiation exposures and subsequent health issues. Although the population differ in radiation quality, dose and timing, consistent findings from case studies have indicated that risks associated with such therapy are of much importance. Despite the fact that therapeutic radiation has multiple benefits, the arising complications such as cardiac diseases and lung cancer cannot be ignored. Though some controversies are evident from the above literature review regarding the detrimental impact of radiation therapy, the majority of the literature evidence point out towards the risks associated with the therapy. Increased knowledge of radiation-related influences has an imperative role in assisting the treatment approach for patients with breast cancer and improving follow-up care. The long-term hazards and health complications in the general population are to be monitored in a direct manner for understanding the extent of the negative impact. The relationship between radiotherapy and health risk has much clinical relevance when it comes to individual screening, modification of risk factor and prevention of diseases. There is an immediate need of advancing our knowledge on the appropriate techniques for patient selection and application of radiation so that therapeutic approach is far more safer. Efforts are to be given continually for reduction of the burden of radiation therapy. Further research based on the gaps of existing literature would surely define optimal management for breast cancer patients after radiation therapy.

 

References

Agrawal, S. (2014). Late effects of cancer treatment in breast cancer survivors. South Asian Journal of Cancer, 3(2), 112–115. https://doi.org/10.4103/2278-330X.130445

Cheng, Y. J., Nie, X. Y., Ji, C. C., Lin, X. X., Liu, L. J., Chen, X. M., ... & Wu, S. H. (2017). Long?Term Cardiovascular Risk After Radiotherapy in Women With Breast Cancer. Journal of the American Heart Association, 6(5), e005633.

Darby, S. C., Ewertz, M., McGale, P., Bennet, A. M., Blom-Goldman, U., Brønnum, D., ... & Jensen, M. B. (2013). Risk of ischemic heart disease in women after radiotherapy for breast cancer. New England Journal of Medicine, 368(11), 987-998.

Eldredge-Hindy, H. B., Rosenberg, A. L., & Simone, N. L. (2014). Intraoperative radiotherapy for breast cancer: the lasting effects of a fleeting treatment. International journal of breast cancer, 2014.

Giordano, S. H., Kuo, Y. F., Freeman, J. L., Buchholz, T. A., Hortobagyi, G. N., & Goodwin, J. S. (2005). Risk of cardiac death after adjuvant radiotherapy for breast cancer. Journal of the National Cancer Institute, 97(6), 419-424.

Grantzau, T., & Overgaard, J. (2015). Risk of second non-breast cancer after radiotherapy for breast cancer: a systematic review and meta-analysis of 762,468 patients. Radiotherapy and Oncology, 114(1), 56-65.

Greenwalt, J. C., Mendenhall, N. P., Kennedy, W. R., Lightsey, J., Morris, C. G., & Bradley, J. A. (2016). Radiation Therapy in the Treatment of Inflammatory Breast Cancer (IBC): A Retrospective Review of IBC Patients. International Journal of Radiation Oncology• Biology• Physics, 96(2), E1-E2.

Haque, R., Yood, M. U., Geiger, A. M., Kamineni, A., Avila, C. C., Shi, J., ... & Quinn, V. P. (2011). Long-term safety of radiotherapy and breast cancer laterality in older survivors. Cancer Epidemiology and Prevention Biomarkers, 20(10), 2120-2126.

Hong, J. C., Rahimy, E., Gross, C. P., Shafman, T., Hu, X., James, B. Y., ... & Soulos, P. R. (2017). Radiation Dose and Cardiac Risk in Breast Cancer Treatment: An Analysis of Modern Radiotherapy Including Community Settings. Practical Radiation Oncology.

Jagsi, R. (2014). Progress and controversies: radiation therapy for invasive breast cancer. CA: a cancer journal for clinicians, 64(2), 135-152.

Jethwa, K. R., Kahila, M. M., Hunt, K. N., Brown, L. C., Corbin, K. S., Park, S. S., ... & Mutter, R. W. (2017). Delineation of Internal Mammary Nodal Target Volumes in Breast Cancer Radiation Therapy. International Journal of Radiation Oncology* Biology* Physics, 97(4), 762-769.

Kaidar-Person, O., Poortmans, P., Kuten, A., & Morgan, D. A. (2015). Radiotherapy for elderly patients with low-risk breast cancer. The Lancet Oncology, 16(5), e196-e197.

Kaufman, E. L., Jacobson, J. S., Hershman, D. L., Desai, M., & Neugut, A. I. (2008). Effect of breast cancer radiotherapy and cigarette smoking on risk of second primary lung cancer. Journal of Clinical Oncology, 26(3), 392-398.

Norman, S. A., Localio, A. R., Kallan, M. J., Weber, A. L., Torpey, H. A. S., Potashnik, S. L., ... & Solin, L. J. (2010). Risk factors for lymphedema after breast cancer treatment. Cancer Epidemiology and Prevention Biomarkers, 1055-9965.

Offersen, B. V., Nielsen, H. M., Jacobsen, E. H., Nielsen, M. H., Krause, M., Stenbygaard, L., ... & Overgaard, J. (2017). Hypo-vs normofractionated radiation therapy of early stage breast cancer in the randomized DBCG HYPO trial. European Journal of Cancer, 72, S9-S10.

Sperk, E., Teich, P. C., Weiß, C., Sütterlin, M., & Wenz, F. (2016). Risk Factors for Breast Cancer Recurrence After Intraoperative Radiation Therapy (IORT). International Journal of Radiation Oncology• Biology• Physics, 96(2), E12.

Taylor, C., Correa, C., Duane, F. K., Aznar, M. C., Anderson, S. J., Bergh, J., ... & Pierce, L. (2017). Estimating the risks of breast cancer radiotherapy: evidence from modern radiation doses to the lungs and heart and from previous randomized trials. Journal of Clinical Oncology, 35(15), 1641-1649.

Tunio, M. A., Al Asiri, M., Bayoumi, Y., Stanciu, L. G., Al Johani, N., & Al Saeed, E. F. (2015). Is thyroid gland an organ at risk in breast cancer patients treated with locoregional radiotherapy? Results of a pilot study. Journal of cancer research and therapeutics, 11(4), 684.

Zeidan, A. M., Long, J. B., Wang, R., Hu, X., James, B. Y., Huntington, S. F., ... & Gross, C. P. (2017). Risk of myeloid neoplasms after radiotherapy among older women with localized breast cancer: A population-based study. PloS one, 12(9), e0184747.

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