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. 2003 Sep-Dec;7(3-4):167–172. doi: 10.1080/13577140310001650330

Radiation-Induced Leiomyosarcoma: Does Antimetabolite Chemotherapy Contribute? A Report of Three Cases

Bruce Brockstein 1,✉, Arno Mundt 2, Daniel J Haraf 2, Mark Ferguson 3, Anthony Montag 4
PMCID: PMC2395527  PMID: 18521382

Abstract

Purpose: Radiation therapy in low and high doses is known to be associated with the occurrence of late secondary sarcomas. The addition of chemotherapy has not been clearly demonstrated as a contributing factor. We describe three patients with radiation-associated leiomyosarcoma who had also received antimetabolite chemotherapy.

Methods: Three cases of leiomyosarcoma occurring 9–27 years after radiation and antimetabolite chemotherapy are presented, along with histopathological details. A Medline search was used to assess prior reports of leiomyosarcoma after radiation.

Results: These three cases appear to be the first reported in which leiomyosarcoma followed therapy with radiation and antimetabolites.

Discussion: With the increasing use of antimetabolite therapy combined with radiation, there is the potential for more occurrences of leiomyosarcoma or other post-treatment sarcomas.

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Selected References

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  1. Amendola B. E., Amendola M. A., McClatchey K. D., Miller C. H., Jr Radiation-associated sarcoma: a review of 23 patients with postradiation sarcoma over a 50-year period. Am J Clin Oncol. 1989 Oct;12(5):411–415. [PubMed] [Google Scholar]
  2. Amichetti M., Boi S. Postirradiation sarcoma in a patient treated for testicular seminoma. Oncology. 1993 Jul-Aug;50(4):264–266. doi: 10.1159/000227192. [DOI] [PubMed] [Google Scholar]
  3. Aoki T., Ozeki Y., Watanabe M., Tanaka S., Isaki H., Terahata S. Development of primary leiomyosarcoma of the sternum postirradiation: report of a case. Surg Today. 1998;28(12):1326–1328. doi: 10.1007/BF02482828. [DOI] [PubMed] [Google Scholar]
  4. Beaty O., 3rd, Hudson M. M., Greenwald C., Luo X., Fang L., Wilimas J. A., Thompson E. I., Kun L. E., Pratt C. B. Subsequent malignancies in children and adolescents after treatment for Hodgkin's disease. J Clin Oncol. 1995 Mar;13(3):603–609. doi: 10.1200/JCO.1995.13.3.603. [DOI] [PubMed] [Google Scholar]
  5. Bhatia S., Robison L. L., Oberlin O., Greenberg M., Bunin G., Fossati-Bellani F., Meadows A. T. Breast cancer and other second neoplasms after childhood Hodgkin's disease. N Engl J Med. 1996 Mar 21;334(12):745–751. doi: 10.1056/NEJM199603213341201. [DOI] [PubMed] [Google Scholar]
  6. Boivin J. F., O'Brien K. Solid cancer risk after treatment of Hodgkin's disease. Cancer. 1988 Jun 15;61(12):2541–2546. doi: 10.1002/1097-0142(19880615)61:12<2541::aid-cncr2820611225>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
  7. Brenin CM, Small W, Jr, Talamonti MS, Gradisher WJ. Radiation-Induced Sarcoma Following Treatment of Breast Cancer. Cancer Control. 1998 Oct;5(5):425–432. doi: 10.1177/107327489800500505. [DOI] [PubMed] [Google Scholar]
  8. Drumea K., Sabo E., Zuckerman E., Naschitz J. E. Leiomyosarcoma of the colon in the aftermath of pelvic irradiation for endometrial carcinoma. Am J Gastroenterol. 1993 Aug;88(8):1302–1302. [PubMed] [Google Scholar]
  9. Folberg R., Cleasby G., Flanagan J. A., Spencer W. H., Zimmerman L. E. Orbital leiomyosarcoma after radiation therapy for bilateral retinoblastoma. Arch Ophthalmol. 1983 Oct;101(10):1562–1565. doi: 10.1001/archopht.1983.01040020564012. [DOI] [PubMed] [Google Scholar]
  10. Font R. L., Jurco S., 3rd, Brechner R. J. Postradiation leiomyosarcoma of the orbit complicating bilateral retinoblastoma. Arch Ophthalmol. 1983 Oct;101(10):1557–1561. doi: 10.1001/archopht.1983.01040020559011. [DOI] [PubMed] [Google Scholar]
  11. Fujii H., Barnes L., Johnson J. T., Kapadia S. B. Post-radiation primary intranodal leiomyosarcoma. J Laryngol Otol. 1995 Jan;109(1):80–83. doi: 10.1017/s0022215100129329. [DOI] [PubMed] [Google Scholar]
  12. Hartley C. Post-irradiation leiomyosarcoma of the maxilla. J Laryngol Otol. 1993 Nov;107(11):1082–1082. doi: 10.1017/s0022215100125356. [DOI] [PubMed] [Google Scholar]
  13. Henry-Amar M. Second cancer after the treatment for Hodgkin's disease: a report from the International Database on Hodgkin's Disease. Ann Oncol. 1992 Sep;3 (Suppl 4):117–128. doi: 10.1093/annonc/3.suppl_4.s117. [DOI] [PubMed] [Google Scholar]
  14. Korbi S., Meyer D., Skalli O., Gabbiani G., Kapanci Y. Post-irradiation leiomyosarcoma. Case report with immunohistochemical studies. J Submicrosc Cytol. 1987 Apr;19(2):365–369. [PubMed] [Google Scholar]
  15. Lalwani A. K., Kaplan M. J. Paranasal sinus leiomyosarcoma after cyclophosphamide and irradiation. Otolaryngol Head Neck Surg. 1990 Dec;103(6):1039–1042. doi: 10.1177/019459989010300627. [DOI] [PubMed] [Google Scholar]
  16. Lee K. H., Fiedler P., Passarelli J., Bobrow S. Autoimmune hemolytic anemia associated with postirradiation malignant stromal tumor (leiomyosarcoma) of the jejunum. Ann Diagn Pathol. 2000 Dec;4(6):367–369. doi: 10.1053/adpa.2000.19373. [DOI] [PubMed] [Google Scholar]
  17. Lieber M. R., Winans C. S., Griem M. L., Moossa R., Elner V. M., Franklin W. A. Sarcomas arising after radiotherapy for peptic ulcer disease. Dig Dis Sci. 1985 Jun;30(6):593–599. doi: 10.1007/BF01320269. [DOI] [PubMed] [Google Scholar]
  18. Lynch D. F., Jr, Herr H. W. Radiation-induced sarcoma following radiotherapy for testicular tumor. J Urol. 1981 Dec;126(6):845–846. doi: 10.1016/s0022-5347(17)54778-3. [DOI] [PubMed] [Google Scholar]
  19. Mark R. J., Poen J., Tran L. M., Fu Y. S., Selch M. T., Parker R. G. Postirradiation sarcomas. A single-institution study and review of the literature. Cancer. 1994 May 15;73(10):2653–2662. doi: 10.1002/1097-0142(19940515)73:10<2653::aid-cncr2820731030>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
  20. Martin-Hirsch D. P., Habashi S., Benbow E. W., Farrington W. T. Post-irradiation leiomyosarcoma of the maxilla. J Laryngol Otol. 1991 Dec;105(12):1068–1071. doi: 10.1017/s0022215100118213. [DOI] [PubMed] [Google Scholar]
  21. Mauch P. M., Kalish L. A., Marcus K. C., Coleman C. N., Shulman L. N., Krill E., Come S., Silver B., Canellos G. P., Tarbell N. J. Second malignancies after treatment for laparotomy staged IA-IIIB Hodgkin's disease: long-term analysis of risk factors and outcome. Blood. 1996 May 1;87(9):3625–3632. [PubMed] [Google Scholar]
  22. Mertens F., Larramendy M., Gustavsson A., Gisselsson D., Rydholm A., Brosjö O., Mitelman F., Knuutila S., Mandahl N. Radiation-associated sarcomas are characterized by complex karyotypes with frequent rearrangements of chromosome arm 3p. Cancer Genet Cytogenet. 2000 Jan 15;116(2):89–96. doi: 10.1016/s0165-4608(99)00105-3. [DOI] [PubMed] [Google Scholar]
  23. Mihara F., Gupta K. L., Kartchner Z. A., Kogutt M. S., Robinson A. E. Leiomyosarcoma after retinoblastoma radiotherapy. Radiat Med. 1991 Sep-Oct;9(5):183–184. [PubMed] [Google Scholar]
  24. Murakami N., Morioka T., Nishio S., Matsukado K., Inamura T., Fukui M., Kouno S. [Radiation-induced leiomyosarcoma of the dura mater: a case report]. No Shinkei Geka. 1997 Nov;25(11):1049–1053. [PubMed] [Google Scholar]
  25. Murray E. M., Werner D., Greeff E. A., Taylor D. A. Postradiation sarcomas: 20 cases and a literature review. Int J Radiat Oncol Biol Phys. 1999 Nov 1;45(4):951–961. doi: 10.1016/s0360-3016(99)00279-5. [DOI] [PubMed] [Google Scholar]
  26. Nyandoto P., Muhonen T., Joensuu H. Second cancer among long-term survivors from Hodgkin's disease. Int J Radiat Oncol Biol Phys. 1998 Sep 1;42(2):373–378. doi: 10.1016/s0360-3016(98)00217-x. [DOI] [PubMed] [Google Scholar]
  27. O'Sullivan S. G., Das Narla L., Ferraro E. Primary ovarian leiomyosarcoma in an adolescent following radiation for medulloblastoma. Pediatr Radiol. 1998 Jun;28(6):468–470. doi: 10.1007/s002470050386. [DOI] [PubMed] [Google Scholar]
  28. Ron E., Lubin J. H., Shore R. E., Mabuchi K., Modan B., Pottern L. M., Schneider A. B., Tucker M. A., Boice J. D., Jr Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies. Radiat Res. 1995 Mar;141(3):259–277. [PubMed] [Google Scholar]
  29. Schneider A. B., Recant W., Pinsky S. M., Ryo U. Y., Bekerman C., Shore-Freedman E. Radiation-induced thyroid carcinoma. Clinical course and results of therapy in 296 patients. Ann Intern Med. 1986 Sep;105(3):405–412. doi: 10.7326/0003-4819-105-3-405. [DOI] [PubMed] [Google Scholar]
  30. Schneider K., Dickerhoff R., Bertele R. M. Malignant gastric sarcoma--diagnosis by ultrasound and endoscopy. Pediatr Radiol. 1986;16(1):69–70. doi: 10.1007/BF02387513. [DOI] [PubMed] [Google Scholar]
  31. Sener S. F., Milos S., Feldman J. L., Martz C. H., Winchester D. J., Dieterich M., Locker G. Y., Khandekar J. D., Brockstein B., Haid M. The spectrum of vascular lesions in the mammary skin, including angiosarcoma, after breast conservation treatment for breast cancer. J Am Coll Surg. 2001 Jul;193(1):22–28. doi: 10.1016/s1072-7515(01)00863-8. [DOI] [PubMed] [Google Scholar]
  32. Sheppard D. G., Libshitz H. I. Post-radiation sarcomas: a review of the clinical and imaging features in 63 cases. Clin Radiol. 2001 Jan;56(1):22–29. doi: 10.1053/crad.2000.0599. [DOI] [PubMed] [Google Scholar]
  33. Stein M. E., Leviov M., Drumea K., Goralnik L., Miselevich I., Kuten A. Radiation-induced sarcoma following curative radiotherapy for testicular seminoma: case report and brief review of the literature. Tumori. 1997 May-Jun;83(3):721–723. doi: 10.1177/030089169708300320. [DOI] [PubMed] [Google Scholar]
  34. Stevens G. N., Tattersall M. H., Stalley P. Leiomyosarcoma following therapeutic irradiation for ankylosing spondylitis. Br J Radiol. 1990 Sep;63(753):730–732. doi: 10.1259/0007-1285-63-753-730. [DOI] [PubMed] [Google Scholar]
  35. Swerdlow A. J., Douglas A. J., Hudson G. V., Hudson B. V., Bennett M. H., MacLennan K. A. Risk of second primary cancers after Hodgkin's disease by type of treatment: analysis of 2846 patients in the British National Lymphoma Investigation. BMJ. 1992 May 2;304(6835):1137–1143. doi: 10.1136/bmj.304.6835.1137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Tucker M. A., Coleman C. N., Cox R. S., Varghese A., Rosenberg S. A. Risk of second cancers after treatment for Hodgkin's disease. N Engl J Med. 1988 Jan 14;318(2):76–81. doi: 10.1056/NEJM198801143180203. [DOI] [PubMed] [Google Scholar]
  37. Tucker M. A., D'Angio G. J., Boice J. D., Jr, Strong L. C., Li F. P., Stovall M., Stone B. J., Green D. M., Lombardi F., Newton W. Bone sarcomas linked to radiotherapy and chemotherapy in children. N Engl J Med. 1987 Sep 3;317(10):588–593. doi: 10.1056/NEJM198709033171002. [DOI] [PubMed] [Google Scholar]
  38. Weatherby R. P., Dahlin D. C., Ivins J. C. Postradiation sarcoma of bone: review of 78 Mayo Clinic cases. Mayo Clin Proc. 1981 May;56(5):294–306. [PubMed] [Google Scholar]
  39. Weiss K. S., Zidar B. L., Wang S., Magovern G. J., Sr, Raju R. N., Lupetin A. R., Shackney S. E., Simon S. R., Singh M., Pugh R. P. Radiation-induced leiomyosarcoma of the great vessels presenting as superior vena cava syndrome. Cancer. 1987 Sep 15;60(6):1238–1242. doi: 10.1002/1097-0142(19870915)60:6<1238::aid-cncr2820600613>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
  40. Yamamura T., Takada A., Higashiyama M., Yoshikawa K. Subcutaneous leiomyosarcoma developing in a radiation dermatitis. Dermatologica. 1991;183(2):154–156. doi: 10.1159/000247659. [DOI] [PubMed] [Google Scholar]
  41. van Leeuwen F. E., Klokman W. J., Hagenbeek A., Noyon R., van den Belt-Dusebout A. W., van Kerkhoff E. H., van Heerde P., Somers R. Second cancer risk following Hodgkin's disease: a 20-year follow-up study. J Clin Oncol. 1994 Feb;12(2):312–325. doi: 10.1200/JCO.1994.12.2.312. [DOI] [PubMed] [Google Scholar]
  42. van Leeuwen F. E., Klokman W. J., Veer M. B., Hagenbeek A., Krol A. D., Vetter U. A., Schaapveld M., van Heerde P., Burgers J. M., Somers R. Long-term risk of second malignancy in survivors of Hodgkin's disease treated during adolescence or young adulthood. J Clin Oncol. 2000 Feb;18(3):487–497. doi: 10.1200/JCO.2000.18.3.487. [DOI] [PubMed] [Google Scholar]

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