Petersen, Ivy A.

10058 Background: P-METs remain illusive with standard treatments for STS. AGM-CSF demonstrated tolerability with promising efficacy in reducing P-METS. We evaluated the 2-yr P-MET free rate in chemonaiive pts with extremity STS. Methods: ECOG PS 0/1 and Gr 3/4 primary STS of the limb girdle/extremities, were required. Treatment sequence: 2 cycles of IMAP (Ifosfamide, Mitomycin, Doxorubicin, Cisplatin) plus s.q. GM-CSF (preload d -6 to -3, d1–14); MAP (d0, 28) during irradiation (d1–35) plus AGM-CSF 250 mcg bid (d1–7, 15- 22, 28–35); surgery; post-op irradiation plus AGM-CSF 250 mcg bid (d1–7, 15–22, 28–35, 42–49). 6 of 35 pts with P-METS in ≤ 2 yrs implied lack of efficacy w.r.t. reducing P-METS. Results: 38 eligible pts were enrolled (20 male, median age 51 yrs, 24 PS 0). Median size of tumor 9 cm (2.3–26.7 cm).Location of tumors included: proximal extremity-16, distal extremity-11, and limb girdle-12. 79% received debulking surgery; 29 rendered disease-free. 38 pts are evaluable for toxicity (see table ). More common Gr 3+ events related to treatment appear below. 79% had Gr 4 neutropenia, despite s.q. GM-CSF. 6 pts have died, with 2.5 yrs median follow-up on survivors (range .4- 4.6). No treatment related fatalities occurred. 10 pts had P-METS ≤ 2 yrs. The estimated 2 yr P-MET free rate is 75% (95% CI 62–91). Conclusions: Although high, neutropenia was as expected. AGM-CSF failed to improve the 2 yr P-MET free rate in this group of STS pts. Other strategies need to be explored. Supported by NIH Grant CA15083–32 and Berlex Corporation. Max Severity (Gr 3+) [Table: see text] No significant financial relationships to disclose.

AbstractBackgroundWe reviewed the disease control and complications of the treatment of sacrococcygeal chordoma from four tertiary cancer centers with emphasis on the effects of radiotherapy in surgically treated patients.MethodsA total of 193 patients with primary sacrococcygeal chordoma from 1990 to 2015 were reviewed. There were 124 males, with a mean age of 59 ± 15 years and a mean follow‐up of 7 ± 4 years. Eighty‐nine patients received radiotherapy with a mean total dose of 61.8 ± 10.9 Gy.ResultsThe 10‐year disease‐free and disease‐specific survival was 58% and 72%, respectively. Radiation was not associated with local recurrence (hazard ratio [HR], 1.13; 95% confidence interval [CI], 0.59‐2.17; P = 0.71), metastases (HR, 0.93; 95% CI, 0.45‐1.91; P = 0.85) or disease‐specific survival (HR, 0.96; 95% CI, 0.46‐2.00; P = 0.91). Higher doses (≥70 Gy; HR, 0.52; 95% CI, 0.20‐1.32; P = 0.17) may be associated with reduced local recurrence. Radiotherapy was associated with wound complications (HR, 2.76; 95% CI, 1.64‐4.82;, P < 0.001) and sacral stress fractures (HR, 4.73; 95% CI, 1.88‐14.38; P < 0.001).ConclusionsIn this multicenter review, radiotherapy was not associated with tumor outcome but associated with complications. The routine use of radiotherapy with en‐bloc resection of sacrococcygeal chordomas should be reconsidered in favor of a selective, individualized approach with a radiation dose of ≥70 Gy.

AbstractPurposeLocal control for Ewing sarcoma (ES) has improved in modern studies. However, it is unclear if these gains have also been achieved for pelvis tumors. The purpose of this study is to evaluate local control and survival in pelvis ES patients treated in the modern era.MethodsAll pelvis ES patients diagnosed from 1990 to 2012 and seen at Mayo Clinic were identified. Factors relevant to survival and local control were analyzed.ResultsThe cohort consisted of 48 patients. Fifty‐two percent had metastatic disease at diagnosis. The 5‐year overall survival and event‐free survival was 73% and 65%, respectively, for localized disease. The 5‐year cumulative incidence of local recurrence was 19%, with a 26% incidence for radiation, 13% for surgery, and 0% for surgery + radiation (P = 0.54). All local failures occurred in‐field. Sacral involvement by tumor trended toward a higher incidence of local recurrence (hazard ratio 3.06, P = 0.09). Patients treated with definitive radiation doses ≥5,600 cGy had a lower incidence of local recurrence (17% vs. 28%, P = 0.61).ConclusionsOur study demonstrates excellent survival for localized tumors in the modern era. Anatomical localization within the pelvis likely correlates with outcomes. Local control remains problematic, especially for patients treated with definitive radiation. Though statistically not significant, surgery + radiation and definitive radiation dose ≥5,600 cGy were associated with the lowest incidence of local failure, suggesting treatment intensification may improve local control for pelvis ES.

Background: Cardiomyocytes are resistant to radiation. However, cardiac radiation exposure causes coronary microvascular endothelial inflammation, a perturbation implicated in the pathogenesis of heart failure (HF) and particularly HF with preserved ejection fraction (HFpEF). Radiotherapy for breast cancer results in variable cardiac radiation exposure and may increase the risk of HF. Methods: We conducted a population-based case-control study of incident HF in 170 female residents of Olmsted County, Minnesota (59 cases and 111 controls), who underwent contemporary (1998–2013) radiotherapy for breast cancer with computed tomography–assisted radiotherapy planning. Controls were matched to cases for age, tumor side, chemotherapy use, diabetes mellitus, and hypertension. Mean cardiac radiation dose (MCRD) in each patient was calculated from the patient’s computed tomography images and radiotherapy plan. Results: Mean age at radiotherapy was 69±9 years. Of HF cases, 38 (64%) had EF≥50% (HFpEF), 18 (31%) had EF<50% (HF with reduced EF), and 3 (5%) did not have EF measured. The EF was ≥40% in 50 of the 56 HF cases (89%) with an EF measurement. The mean interval from radiotherapy to HF was 5.8±3.4 years. The odds of HF was higher in patients with a history of ischemic heart disease or atrial fibrillation. The MCRD was 2.5 Gy (range, 0.2–13.1 Gy) and higher in cases (3.3±2.7 Gy) than controls (2.1±2.0 Gy; P =0.004). The odds ratio (95% confidence interval) for HF per log MCRD was 9.1 (3.4–24.4) for any HF, 16.9 (3.9–73.7) for HFpEF, and 3.17 (0.8–13.0) for HF with reduced EF. The increased odds of any HF or HFpEF with increasing MCRD remained significant after adjustment for HF risk factors and in sensitivity analyses matching by cancer stage rather than tumor side. Only 18.6% of patients experienced new or recurrent ischemic events between radiotherapy and the onset of HF. Conclusions: The relative risk of HFpEF increases with increasing cardiac radiation exposure during contemporary conformal breast cancer radiotherapy. These data emphasize the importance of radiotherapy techniques that limit MCRD during breast cancer treatment. Moreover, these data provide further support for the importance of coronary microvascular compromise in the pathophysiology of HFpEF.

Background:Myoepithelioma of the soft tissues is a rare entity and little is known about how best to manage locally recurrent and high-grade disease. Here, we retrospectively examined outcomes of surgery, chemotherapy, and radiation therapy (RT) for treatment of low-grade and high-grade myoepithelioma of soft tissues.Methods:We reviewed 20 cases of myoepithelioma of soft tissues seen at Mayo Clinic between 1994 and 2014. The effect of histologic grade and therapies received on relapse and survival were assessed.Results:We identified 13 patients with low-grade disease and 7 patients with high-grade disease. We found that low-grade disease was frequently effectively managed with surgical resection alone, whereas high-grade disease frequently metastasized and was often fatal. The 5-year event-free survival was 88% (confidence interval, 46%-98%) for low-grade disease versus 36% (confidence interval, 7%-75%;P=0.04) for high-grade disease. The relapse rate in low-grade disease was 29% at 5 years versus 64% (P=0.04) in high-grade disease. No significant responses to chemotherapy were noted, however, excellent responses to perioperative RT were seen.Conclusions:Surgery continues as the primary modality of treatment for myoepithelioma of soft tissues. Our study did not show a clear benefit of chemotherapy in the metastatic disease setting, but supports the use of perioperative RT in the management of high-grade disease; further investigation is warranted.

Purpose We performed a multi-institutional prospective phase II trial to assess late toxicities in patients with extremity soft tissue sarcoma (STS) treated with preoperative image-guided radiation therapy (IGRT) to a reduced target volume. Patients and Methods Patients with extremity STS received IGRT with (cohort A) or without (cohort B) chemotherapy followed by limb-sparing resection. Daily pretreatment images were coregistered with digitally reconstructed radiographs so that the patient position could be adjusted before each treatment. All patients received IGRT to reduced tumor volumes according to strict protocol guidelines. Late toxicities were assessed at 2 years. Results In all, 98 patients were accrued (cohort A, 12; cohort B, 86). Cohort A was closed prematurely because of poor accrual and is not reported. Seventy-nine eligible patients from cohort B form the basis of this report. At a median follow-up of 3.6 years, five patients did not have surgery because of disease progression. There were five local treatment failures, all of which were in field. Of the 57 patients assessed for late toxicities at 2 years, 10.5% experienced at least one grade ≥ 2 toxicity as compared with 37% of patients in the National Cancer Institute of Canada SR2 (CAN-NCIC-SR2: Phase III Randomized Study of Pre- vs Postoperative Radiotherapy in Curable Extremity Soft Tissue Sarcoma) trial receiving preoperative radiation therapy without IGRT (P < .001). Conclusion The significant reduction of late toxicities in patients with extremity STS who were treated with preoperative IGRT and absence of marginal-field recurrences suggest that the target volumes used in the Radiation Therapy Oncology Group RTOG-0630 (A Phase II Trial of Image-Guided Preoperative Radiotherapy for Primary Soft Tissue Sarcomas of the Extremity) study are appropriate for preoperative IGRT for extremity STS.