Assessment of Secondary Sarcomas Among Patients With Cancer of the Abdomen or Pelvis Who Received Combinations of Surgery, Radiation, and Chemotherapy vs Surgery Alone
Authors: Amanda E. Hird, Diana E. Magee, Rano Matta, Refik Saskin, Erind Dvorani, Girish S. Kulkarni, Ronald Kodama, Sender Herschorn, Steven A. Narod, Robert K. Nam
Journal: JAMA Network Open (2020)

<h3>Importance</h3> The association of radiation and chemotherapy with the development of secondary sarcoma is known, but the contemporary risk has not been well characterized for patients with cancers of the abdomen and pelvis. <h3>Objective</h3> To compare the risk of secondary sarcoma among patients treated with combinations of surgery, radiation, or chemotherapy with patients treated with surgery alone and the general population. <h3>Design, Setting, and Participants</h3> This population-based cohort study included 173 580 patients in Ontario, Canada, with nonmetastatic cancer of the prostate, bladder, colon, rectum or anus, cervix, uterus, or testis. Patients were enrolled from January 1, 2002, to January 31, 2017. Data analysis was conducted from March 1, 2019, to January 31, 2020. <h3>Exposures</h3> Treatment combinations of radiation, chemotherapy, and surgery. <h3>Main Outcome and Measures</h3> Diagnosis of sarcoma based on histologic codes from the Ontario Cancer Registry. Time to sarcoma was compared using a cause-specific proportional hazard model. <h3>Results</h3> Of 173 580 patients, most were men (125 080 [72.1%]), and the largest group was aged between 60 and 69 years (58 346 [33.6%]). Most patients had genitourinary cancer (86 235 [51.4%]) or colorectal cancer (69 241 [39.9%]). Overall, 64 301 (37.1%) received surgery alone, 51 220 (29.5%) received radiation alone, 15 624 (9.0%) were treated with radiation and chemotherapy, 15 252 (8.8%) received radiation with surgery, and 11 822 (6.8%) received all 3 treatments. A total of 332 patients (0.2%) had sarcomas develop during a median (interquartile range) follow-up of 5.7 (2.2-8.9) years. The incidence of sarcoma was 0.3% among those who underwent radiation alone (138 of 51 220) and radiation with chemotherapy (40 of 15 624), 0.2% among those who received radiation and surgery (36 of 15 252) and all 3 modalities (25 of 11 822), and 0.1% among those who received surgery with chemotherapy (13 of 14 861) and surgery alone (80 of 64 801). Compared with a reference group of patients who had surgery alone, the greatest risk of sarcoma was found among patients who underwent a combination of radiation and chemotherapy (cause-specific relative hazard [csRH], 4.07; 95% CI, 2.75-6.01;<i>P</i> &lt; .001), followed by patients who had radiation alone (csRH, 2.35; 95% CI, 1.77-3.12;<i>P</i> &lt; .001), radiation with surgery (csRH, 2.33; 95% CI, 1.57-3.46;<i>P</i> &lt; .001), and all 3 modalities (csRH, 2.27; 95% CI, 1.44-3.58;<i>P</i> &lt; .001). In the general population, 7987 events occurred during 46 554 803 person-years (17.2 events per 100 000 person-years). The standardized incidence ratio for sarcoma among patients treated with radiation compared with the general population was 2.41 (95% CI, 1.57-3.69; 41.3 events per 100 000 person-years). The annual number of cases of sarcoma increased from 2009 (15 per 100 000 persons) to 2016 (32 per 100 000 persons), but the annual rate did not change during the study period. <h3>Conclusions and Relevance</h3> In this cohort study, patients treated with radiation or chemotherapy for abdominopelvic cancers had an increased rate of sarcoma. Although the absolute rate is low, patients and physicians should be aware of this increased risk of developing sarcoma.