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• W3159012362 abstract "HomeRadioGraphicsVol. 41, No. 3 PreviousNext Radiation OncologyFree AccessInvited Commentary: Secondary Malignancies in Patients Treated with Radiation TherapyAnna Shapiro Anna Shapiro Author AffiliationsFrom the Department of Radiation Oncology, State University of New York Upstate Medical University, 750 E Adams St, Syracuse, NY 13210-2306.Address correspondence to the author (e-mail: [email protected]).Anna Shapiro Published Online:Apr 23 2021https://doi.org/10.1148/rg.2021210028MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In See also the article by Khanna et al in this issue.The article by Khanna et al (1) is a timely and comprehensive review of the literature, with a focus on radiation therapy and associated secondary malignancies. These cases are statistically rare but are devastating when they do occur. The incidence of second primary malignancies among cancer survivors appears to be on the rise (2). It has been suggested that their incidence has been underestimated because of limited follow-up of patients with cancer, which is typically 5–10 years. Most radiation therapy–induced malignancies have a latency period of 5–50 years, which is much longer than typical cancer follow-up. In addition, substantial innovations in cancer treatment over the past few decades have led to improved survival rates. Because our patients are living longer, they are encountering more treatment-related complications.Identifying the true incidence of radiation-induced malignancies is challenging. One of the difficulties is in differentiating radiation-induced malignancies from second primary malignancies that occur in cancer survivors, who are known to have more cancers when compared with the general population. This difference could be related to several factors that may have contributed to the development of the first cancer, including genetic predisposition, smoking, obesity, or exposure to environmental toxins. The higher rate of detection of early-stage cancers may be the result of the follow-up and regular imaging to which patients with cancer are subjected. Depending on the site of the disease (eg, cancer of the prostate), comparison of patients treated with radiation to those treated with surgery alone is possible. This may help us to estimate treatment-induced malignancy rates with greater accuracy. In most disease sites at which multidisciplinary treatment is necessary, such comparisons are not possible. As Khanna et al (1) keenly point out, many treatment-induced malignancies are associated with unique genetic signatures. As our understanding of the genetic profile of various tumors expands, next-generation sequencing and other genomic tools are increasingly important in the establishment of the relationship between radiation and the development of secondary malignancy.Many factors contribute to the risk of second malignancy, such as age at the time of treatment, hormonal influences, use of chemotherapy, environmental influences, genetic predisposition, and immunosuppression. A dose-response relationship between radiation exposure and induction of malignancy has been well established clinically and in experimental models. A threshold dose for induction of cancer and the shape of the dose-response curve for higher radiation exposure are not well established. In an effort to alter this risk, radical changes in the philosophy of radiation therapy have taken place over the last few decades.Radiation techniques have shifted from maximum tolerable doses to minimal effective doses, smaller treatment fields, and more conformal deposition of doses. Patients with Hodgkin lymphoma have benefited tremendously from these changes. In the 1980s, the European Organization for Research and Treatment of Cancer (EORTC) proposed a strategy to tailor the degree of aggressiveness of treatment in both chemotherapy and radiation to that of the disease on the basis of the number of prognostic factors. Because of these efforts, radiation fields were decreased from mantle or inverted-Y fields to targeting of involved nodes only. This reduction in volume of healthy tissue in the high-dose range should diminish the incidence of radiation-induced malignancy (3).Similar efforts have also been made in breast cancer, where partial breast radiation is used as an alternative to whole breast radiation in the early stages of breast cancer (4). Motion management techniques have been extremely effective in patients with lung and liver cancers in an effort to minimize the amount of healthy tissue that is exposed to high-dose radiation (5).Further efforts to make radiation fields tighter have driven a shift from three-dimensional conformal radiation therapy to intensity-modulated radiation therapy. This technique involves more fields and a larger volume of healthy tissue that is exposed to lower doses. In addition, the number of monitor units is increased by a factor of two to three, increasing the amount of total-body exposure because of leakage of radiation (6). Both factors can increase the risk for second cancers; however, authors of clinical studies with short follow-up have not corroborated this hypothesis (7).In children, this risk could be higher than in adults, justifying current development of proton therapy, with priority given to this population. Only longer follow-up will allow a true assessment of the real effect of these modern techniques on radiation-induced carcinogenesis.Historically, radiation has been used to treat various benign diseases. Rheumatologic, infectious, and dermatologic conditions were treated with low-dose radiation therapy, which after years led to solid and hematologic malignancies. Because of the longer survival time of these patients, they get an adequate latency period to develop secondary malignancies. Although we still see referrals for heterotopic ossification, keloids, and Dupuytren contracture, beneficial and detrimental effects of radiation therapy should always be confronted, and all efforts should be made to reduce the risks.All patients with a history of radiation exposure require vigilant long-term follow-up to detect secondary cancers early, given the aggressive nature of this disease. Cancer survivorship programs have been established widely and are used for this purpose. The value of good clinical examination cannot be underestimated. Most patients with angiosarcoma of the breast (one of the most common radiation-induced malignancies) present with some form of skin finding (eg, ill-defined discolored patches, ulcerations, eczema, or nonpigmented macules). As Khanna et al (1) describe, mammography, US, and MRI can be helpful in defining the extent of the disease. Multiple skin biopsies with a high index of suspicion are keys to diagnosis (8,9). In other disease sites, clinical examination may not be as revealing, and surveillance imaging is pivotal to follow-up of these patients. Radiologists who are equipped with the knowledge of a patient history of radiation exposure must be knowledgeable of the spectrum of secondary cancers and facilitate early diagnosis, localization, and staging.The author has disclosed no relevant relationships.References1. Khanna L, Prasad SR, Yedururi S, et al. Second malignancies after radiation therapy: update on pathogenesis and cross-sectional imaging findings. RadioGraphics 2021;41(3):876–894. Link, Google Scholar2. Tubiana M. Can we reduce the incidence of second primary malignancies occurring after radiotherapy? A critical review. Radiother Oncol 2009;91(1):4–15; discussion 1–3. Crossref, Medline, Google Scholar3. Suit H, Goldberg S, Niemierko A, et al. Secondary carcinogenesis in patients treated with radiation: a review of data on radiation-induced cancers in human, non-human primate, canine and rodent subjects. Radiat Res 2007;167(1):12–42. Crossref, Medline, Google Scholar4. Hepel JT, Wazer DE. Partial Breast Irradiation Is the Preferred Standard of Care for a Majority of Women With Early-Stage Breast Cancer. J Clin Oncol 2020;38(20):2268–2272. Crossref, Medline, Google Scholar5. Molitoris JK, Diwanji T, Snider JW 3rd, et al. Advances in the use of motion management and image guidance in radiation therapy treatment for lung cancer. J Thorac Dis 2018;10(Suppl 21):S2437–S2450. Crossref, Medline, Google Scholar6. Hall EJ, Wuu CS. Radiation-induced second cancers: the impact of 3D-CRT and IMRT. Int J Radiat Oncol Biol Phys 2003;56(1):83–88. Crossref, Medline, Google Scholar7. Chargari C, Goodman KA, Diallo I, et al. Risk of second cancers in the era of modern radiation therapy: does the risk/benefit analysis overcome theoretical models? Cancer Metastasis Rev 2016;35(2):277–288. Crossref, Medline, Google Scholar8. Hodgson NC, Bowen-Wells C, Moffat F, Franceschi D, Avisar E. Angiosarcomas of the breast: a review of 70 cases. Am J Clin Oncol 2007;30(6):570–573. Crossref, Medline, Google Scholar9. Cozen W, Bernstein L, Wang F, Press MF, Mack TM. The risk of angiosarcoma following primary breast cancer. Br J Cancer 1999;81(3):532–536. Crossref, Medline, Google ScholarArticle HistoryReceived: Feb 10 2021Accepted: Feb 11 2021Published online: Apr 23 2021Published in print: May 2021 FiguresReferencesRelatedDetailsAccompanying This ArticleSecond Malignancies after Radiation Therapy: Update on Pathogenesis and Cross-sectional Imaging FindingsApr 23 2021RadioGraphicsRecommended Articles Breast Cancer Tumor Board: A Radiologist’s Guide to Postmastectomy Radiation TherapyRadioGraphics2023Volume: 43Issue: 3Case 242: Radiation-induced AngiosarcomaRadiology2017Volume: 283Issue: 3pp. 909-916Second Malignancies after Radiation Therapy: Update on Pathogenesis and Cross-sectional Imaging FindingsRadioGraphics2021Volume: 41Issue: 3pp. 876-894Radiofrequency Ablation of Breast Cancer: A Step ForwardRadiology2018Volume: 289Issue: 2pp. 325-326Invited Commentary: Breast Cancer Risk Assessment and Screening Strategies—What’s New?RadioGraphics2020Volume: 40Issue: 4pp. 937-940See More RSNA Education Exhibits Breast Radiotherapy: What the Breast Radiologist Should KnowDigital Posters2019Radio-Induced Malignancies in the Breast: Essentials for the Breast RadiologistDigital Posters2020Radiation-Induced Malignancies: Current Update on Pathogenesis and Cross-Sectional Imaging FindingsDigital Posters2019 RSNA Case Collection Secondary Angiosarcoma of the BreastRSNA Case Collection2021Cutaneous Angiosarcoma of the BreastRSNA Case Collection2021Inflammatory breast cancerRSNA Case Collection2020 Vol. 41, No. 3 Metrics Altmetric Score PDF download" @default.
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