Understanding Radiation-Induced Malignancies: A Two-Edged Sword?

Radiotherapy has long been established as one of the most useful mechanisms in handling cases of cancer. This treatment modality aims at delivering high-energy radiation to malignant cells in a bid to kill or at least impair them to stop their proliferation and formation of tumors. Nevertheless, it has been observed that radiotherapy is a popular approach whose effectiveness cannot be undermined as it is used to treat many types of cancer. but some risks come with its use. Among these, there is a group of dangers that may be truly life-threatening and need immediate treatment or follow-up care; the worst of these difficulties is radiation-induced malignancy and RIMs. By being brought about by the cancer therapy that seeks to heal or contain the primary disease, these secondary cancers are bittersweet for cancer therapy. In reality, radiotherapy is still a life-saving treatment that comes with the risk of secondary malignancies, thus adding to challenges in the long-term management of cancer survivors. This article focuses on elucidating the topic of secondary cancer development, modifiable and non-modifiable risk factors associated with radiation malignancies, and efforts being made to reduce the risk of modern-day cancer therapy.

The Dual Nature of Radiotherapy

Radiotherapy, on the other hand, makes use of ionizing radiation to affect cancer cells and damage their DNA strands. This makes it most useful against rapidly proliferating tissues or cells because, in their case, cancerous cells are usually much more sensitive to radiation than normal cells. However, this mechanism is not without risk, which can be seen in the next paragraph. Unfortunately, radiotherapy is directed at killing cancerous tissues, and this means that healthy neighboring tissues are also destroyed. The long-term effect of ionizing on healthy cells is that over time they get mutated to become malignant, thus causing secondary cancers.

An example of this is the so-called ‘radiation-induced malignancy’ which presents its own set of problems. With discoveries in handling cancer, patients are living longer only to be threatened by other cancer diseases that are a result of radiation exposure. It has been found that the risk of developing another malignancy is highest in patients who had radiotherapy for prostate, breast, and lymphatic system cancers and more, among other types of cancer. Such duality of radiotherapy, which on the one hand acts as a lawful treatment for cancer and, on the other hand, may lead to secondary malignancies, makes its clinical application highly questionable.

Mechanisms Behind Radiation-Induced Malignancies

The ways through which radiation triggers the development of secondary cancers are explained by the DNA injury that radiotherapy has on the malignant as well as nonmalignant cells. Ionizing radiation causes the breaking of the DNA strands within cells, and this is followed by the formation of mutations that will either end up killing the damaged cell or, in the worst case, transform it into a cancerous cell. Radiation is capable of inducing changes in DNA replication, chromosomal alterations, and mutations or alterations in gene expression. Although the human body has its natural ways of fixing this problem; at times, the repair is only partial and imprecise, and what you are left with are mutated cells that may turn into malignant tumors in the long run.

Similar to other malignancies, the appearance of radiation-induced malignancies depends on such factors as the doses of radiation, irradiated tissues’ volume, and the age and genetic profile of the patient. Radiation dose per fraction is inversely propositioned with lateral voltage in that raising the dose per fraction boosts the chances of cellular injury, and exposure of a bigger volume of tissue to radiation raises the number of cells in jeopardy. Further, the cancers are more likely to be induced in children, those with divided cells that are dividing rapidly, and more so given the fact that they have a longer life length so as the secondary cancers to develop.

Yearwise Publication Trend on radiation induced malignancies

Find publication trends on relevant topics

Epidemiology and Types of Radiation-Induced Malignancies

Secondary cancers occur, albeit at a low frequency about the total number of patients treated with radiation therapy, but are rather worrisome because they develop years later and are life-threatening. It has been established that there is a likelihood of incurring secondary cancer for a long time, perhaps several years or decades, after undergoing radiation therapy. For instance, radiotherapy for treating prostate cancer increases the probability of getting colorectal cancers in the regions that were exposed to radiation, such as the rectum and the sigmoid colon. Similarly, women suffering from breast cancer and treated with radiation are at a higher risk of developing lung and heart cancers because the heart and lungs are organs located in proximity to the breast, and radiation therapy affects them as well.

The most frequently diagnosed secondary cancers are those of tissues that are in direct contact with radiation, and this includes skin, bones, and GI tracts. Some of the side effects have included secondary bladder and rectal cancers where radiotherapy has been undertaken for the treatment of other cancers such as those occurring within the pelvic cavity. It also used to be observed that patients with hematologic malignancies like leukemia and lymphoma are seen often and especially in patients who have been exposed to massive radiation that affected the bone marrow radiation; nevertheless, sarcomas—the cancers of bones and connective tissue—can also develop in the irradiated areas, although these are rarer, and they usually develop only after such a high level of radiation or after a long exposure.

Risk Factors and Contributing Variables

Factors that affect radiation-induced malignancies include: There are so many factors, and most of them are unique to the patient and their treatment regimen. The total dose per fraction, or total dose of radiation given during treatment, is also one of the most important considerations. A study also shows that exposure to large doses of radiation enhances the risk of getting another type of cancer. Furthermore, it should be pointed out that the type of radiation that is employed in treatment may matter as well, as other types of radiation, in particular, have higher LET and tend to cause more severe DNA damage.

As to the risk factors, it is also important to consider the age of the patient when he or she was exposed to radiation. Secondary cancers are more common in young patients because growing tissues have a higher rate of cell division, while radiation-induced malignancies can appear a long time after the initial treatment. There are other factors, including genetic factors; human beings who inherit some adjustments in their DNA, for instance, in DNA repair, that make them sensitive to radiation that has mutagenic effects.

Smoking in particular is a severe risk factor for secondary cancers among patients who have received radiotherapy, in addition to other determining factors, lifestyle. For instance, patients who smoke and who are treated with radiation therapy for lung or head-and-neck cancer are 2 to 3 times more likely to develop new cancers in the irradiated areas. This goes a long way to show the need to embrace smoking control and other preventions to avoid the long-term effects of radiotherapy.

Recent Publications on radiation induced malignancies

Find publications on relevant topics

Modern Approaches to Reducing Radiation-Induced Malignancies

However, great progress has been expressed in years belonging to radiotherapy used in the reduction of radiation-induced malignancies. Perhaps one of the most potential approaches is proton beam therapy, where a smaller amount of radiation is administered to the surrounding healthy tissues. Some studies indicate that proton therapy brings lower risks of secondary malignancies as compared to conventional radiation therapies, especially to pediatric cancer patients who are more sensitive to the effects of radiation.

Another method that is getting popular is intensity-modulated radiation therapy, or IMRT to be specific, because it provides a radiation beam to the tumor with high intensity while at the same time sparing the healthy tissues. Of all the applications of IMRT, the use in cancers around crucial structures has been felt most due to its ability to lessen the amount of injury given to such surrounding organs as the bladder and rectum in prostate cancer.

There has also been improvement in the delivery of radiation through imaging, hence minimizing secondary cancers. Some of the newer techniques include Vernacular modulated Arc Therapy or VMAT, and Image-Guided Radiation Therapy, or IGRT. When delivering the radiation, the physician can see where the tumor is located at any given time, and using this ability, make sure that only the tumor is affected as much as possible and the healthy tissues and organs are not affected too much.

The Role of Patient Monitoring and Follow-Up

Because the cancers caused by radiation are mostly indolent, close follow-up of patients who have received radiotherapy is important. It stresses the need to conduct screening for the development of second primary cancers, with particular emphasis on the high-risk regions where early detection will enhance treatment. Possible adverse effects of undergoing the treatment and the need for patients to quit smoking to lower the risk factor should be explained to the patients.

For patients with a history of inherited cancer syndromes or a family history of cancer, there is an increased risk of developing cancer, especially if the patient has a BRCA1 or BRCA2 gene mutation. Then one has to be very cautious when using radiotherapy. Such patients may opt for other therapies, which are believed to harbor minimal potential for developing secondary cancers.

Conclusion

Second, radiation-induced malignancies are among the most serious long-term hazards of cancer treatment. Despite its effectiveness and importance, radiotherapy can lead to the development of second cancers, which is also worth considering. Radiation technology has continued to improve in the recent past, and coupled with the implementation of individualized treatment plans and close follow-up, there is hope that the risks outlined above can be reduced while at the same time enhancing the benefits of radiotherapy. Focusing on the problem of radiation-induced malignancies, it can be stated that for cancer survivors, being aware of the risk is half the battle: they should start practicing healthy behaviors and regularly visiting the doctor.

References

  1. Harbron, R.W. and Pasqual, E., 2020. Ionising radiation as a risk factor for lymphoma: a review. Journal of Radiological Protection40(4), p.R151.
  2. Singh, G.K., Yadav, V., Singh, P. and Bhowmik, K.T., 2017. Radiation-induced malignancies making radiotherapy a “two-edged sword”: a review of literature. World journal of oncology8(1), p.1.
  3. Rapiti, E., Fioretta, G., Verkooijen, H.M., Zanetti, R., Schmidlin, F., Shubert, H., Merglen, A., Miralbell, R. and Bouchardy, C., 2008. Increased risk of colon cancer after external radiation therapy for prostate cancer. International journal of cancer123(5), pp.1141-1145.
  4. Wang, R., Zeidan, A.M., Yu, J.B., Soulos, P.R., Davidoff, A.J., Gore, S.D., Huntington, S.F., Gross, C.P. and Ma, X., 2017. Myelodysplastic syndromes and acute myeloid leukemia after radiotherapy for prostate cancer: a population‐based study. The Prostate77(5), pp.437-445.
  5. Hamdy, F.C., Donovan, J.L., Lane, J.A., Mason, M., Metcalfe, C., Holding, P., Davis, M., Peters, T.J., Turner, E.L., Martin, R.M. and Oxley, J., 2016. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. New England Journal of Medicine375(15), pp.1415-1424.
  6. Pisansky, T.M., 2006. External-beam radiotherapy for localized prostate cancer. New England Journal of Medicine355(15), pp.1583-1591.
  7. Journy, N.M., Morton, L.M., Kleinerman, R.A., Bekelman, J.E. and de Gonzalez, A.B., 2016. Second primary cancers after intensity-modulated vs 3-dimensional conformal radiation therapy for prostate cancer. JAMA oncology2(10), pp.1368-1370.
  8. Pawlish, K.S., Schottenfeld, D., Severson, R. and Montie, J.E., 1997. Risk of multiple primary cancers in prostate cancer patients in the Detroit metropolitan area: a retrospective cohort studyThe Prostate33(2), pp.75-86.

Top Experts on “radiation induced malignancies