Assessment of Secondary Sarcomas Among Patients With Cancer of the Abdomen or Pelvis Who Received Combinations of Surgery, Radiation, and Chemotherapy vs Surgery Alone.

Importance: 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. Objective: 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. Design, Setting, and Participants: 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. Exposures: Treatment combinations of radiation, chemotherapy, and surgery. Main Outcome and Measures: Diagnosis of sarcoma based on histologic codes from the Ontario Cancer Registry. Time to sarcoma was compared using a cause-specific proportional hazard model. Results: 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; P < .001), followed by patients who had radiation alone (csRH, 2.35; 95% CI, 1.77-3.12; P < .001), radiation with surgery (csRH, 2.33; 95% CI, 1.57-3.46; P < .001), and all 3 modalities (csRH, 2.27; 95% CI, 1.44-3.58; P < .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. Conclusions and Relevance: 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.

Pelvic Leiomyosarcoma With Splenic Metastasis and Response Assessment by 18F-FDG PET/CT.

The pelvis is a rare site for the origin of soft tissue sarcomas, and leiomyosarcoma remains the most common soft tissue sarcoma arising in the pelvis. Pelvic leiomyosarcomas are frequently aggressive tumors, and metastatic recurrence rates are high, with the lung, peritoneum, bone, and liver being the most frequent sites. We describe the findings of serial F-FDG PET/CT in a 53-year-old woman having pelvic leiomyosarcoma with uncommon site of metastasis, emphasizing the role of F-FDG PET/CT in response assessment.

Complications and toxicity after abdominal and pelvic hypoxic stop-flow perfusion chemotherapy: incidence and assessment of risk factors.

BACKGROUND: Controversial results regarding the efficacy and toxicity of hypoxic abdominal and pelvic stop-flow perfusion chemotherapy (SFP) have been reported in relatively small series. Hence, because adequate assessment of its benefit in large homogenous cohorts is missing, acceptable morbidity should initially be assured in a series of adequate size. Additionally, risk factors should be assessed for eventual patient selection. METHODS: The morbidity of abdominal and pelvic SFP performed on a miscellaneous group of patients in our institute was analyzed and potential risk factors for adverse events were evaluated. RESULTS: Seventy abdominal (n = 42) and pelvic (n = 28) SFP were performed on 55 patients. In total, 28 adverse effects were observed after 30% of the procedures. Severe (grade 3) adverse events were recorded only after 4% of the procedures, while treatment-related life-threatening events and deaths were not present. Abdominal procedures when compared with pelvic ones were associated with increased systemic toxicity (36 vs. 7%, p = 0.005). Advanced age, gender, prior chemotherapy and/or radiotherapy, limited experience, repeated procedure, drug choice and omission of hemofiltration after SFP completion were not associated with statistically significant increase of procedures with overall or systemic adverse events. CONCLUSIONS: In the present series, abdominal and pelvic SFP was associated with an acceptable morbidity, which was mostly mild or moderate. Abdominal procedures were associated with increased toxicity. This procedure seems to be repeatable and also well tolerated both by elderly patients and by patients who had undergone prior chemotherapy and/or radiotherapy, while hemofiltration does not appear to decrease the incidence of systemic toxicity.

Late effects of pelvic rhabdomyosarcoma and its treatment in female survivors.

PURPOSE: To document the spectrum and severity of late effects in female survivors of pelvic rhabdomyosarcoma. PATIENTS AND METHODS: We reviewed the demographic, diagnostic, treatment, and outcome data of the 26 females treated for pelvic rhabdomyosarcoma at our institution between March 1962 and December 1996 who survived free of disease for 5 or more years. Adverse effects that occurred 5 or more years after diagnosis were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. RESULTS: The most common tumor sites were vagina (n = 7), pelvis/retroperitoneum (n = 6), and bladder (n = 4). All patients received chemotherapy (alkylating agent, n = 23; doxorubicin, n = 16); 22 received radiotherapy (median dose, 46 Gy). Median follow-up of the 23 survivors was 20.3 years. Late effects occurred in 24 patients, 23 of whom had grade 3/4 late effects (median grade 3/4 late effects per patient, three; range, zero to 14). Fourteen patients (54%) required surgery for late complications. The 22 patients who had received radiotherapy had a greater median number of late effects per patient than did the remaining four (9.5 v one; P = .002). The median number of late effects per patient was higher in the 12 patients treated during or after 1984 than in the 14 treated earlier (12.5 v 6.5; P = .041). CONCLUSION: The burden of late effects in girls treated for pelvic rhabdomyosarcoma is significant and does not seem to be diminishing with advances in treatment. Prospective studies are needed to better assess the impact of these late effects on quality of life and functional outcome, and to refine the treatment approach to pelvic rhabdomyosarcoma.

Assessment of chemosensitivity in patients with osteogenic sarcoma using the doxorubicin binding assay.

BACKGROUND AND OBJECTIVES: Assessment of chemosensitivity in patients with osteosarcoma may help identify those with resistance to chemotherapy. In this study, we investigated the clinical value of the doxorubicin binding assay in its ability to identify patients with drug resistance. METHODS: We tested tumor tissue samples obtained at biopsy of 24 patients with high-grade osteosarcoma aged 9-61 years (mean 19.2) for sensitivity to doxorubicin, using the doxorubicin binding assay. Tumor excision was performed in these patients after neoadjuvant chemotherapy. Chemotherapy response was judged on the basis of tumor necrosis achieved and was compared with doxorubicin sensitivity in each of these patients. RESULTS: Doxorubicin sensitivity was good in 15 and poor in 9 of 24 patients studied. In patients with good sensitivity (n = 15), 9 (60%) exhibited a good response to chemotherapy while response was poor in 6. In patients with poor sensitivity (n = 9), response to chemotherapy was poor in all 9 (100%) patients and 7 (77.8%) of these patients developed metastatic disease within a mean period of 5.2 months, resulting in two deaths. The results were statistically significant at P = 0.0193. CONCLUSIONS: Doxorubicin binding assay may be useful in identifying patients with inherent resistance to chemotherapy. As the outcome of patients showing resistance to doxorubicin is poor, innovative strategies may need to be developed for this group of patients.

Postirradiation changes in the pelvis: assessment with MR imaging.

Magnetic resonance (MR) imaging features of pelvic radiation change were assessed in 51 patients and were correlated with tumor and critical tissue radiation dose, time after treatment, and clinical symptoms. The severity of MR tissue changes was graded. Radiation tissue toxicity increased significantly when the dose exceeded 4,500 cGy, with the incidence of marked bladder and rectal changes rising from 8% to 51% and from 24% to 48%, respectively. Similar dose-related changes were seen in other pelvic organs. All grades of tissue change were seen in the bladder and rectum regardless of the time from start of therapy. All patients who exhibited clinical grade 2 or 3 bladder and rectal changes showed moderate or severe changes on MR images. In asymptomatic patients, minimal MR changes were seen in the bladder (47%) and in the rectum (33%). The accuracy of MR imaging in differentiating between radiation damage and residual/recurrent tumor varied with the primary tumor site, being excellent for recurrent cervical cancer and less so for rectal carcinoma.