Citations

AbstractPurposeTo evaluate patterns of failure after multimodality treatment of nongerminomatous germ cell tumors (NGGCTs).Materials and methodsWe retrospectively reviewed records of 34 patients diagnosed with primary intracranial NGGCT between 1988 and 2014.ResultsThirty‐four patients received induction chemotherapy followed by radiation with or without surgery. Median follow‐up was 11.1 years (0.8–23.3). Outcomes were significantly improved in these 34 patients (5‐year overall survival [OS]: 88% versus 50%, P = 0.0092), so analysis is restricted to that subset. Disease‐free survival (DFS) was 67, 60, and 54% at 5, 10, and 15 years, respectively. Elevated cerebrospinal fluid–α‐fetoprotein (CSF–AFP) at diagnosis was associated with poorer DFS (37 vs. 89% at 10 years; P = 0.01). There was no statistically significant difference in OS, or DFS, or patterns of failure for limited radiotherapy volumes versus larger volumes; however, patients receiving initial local radiotherapy had 32% distant central nervous system (CNS) recurrence at 10 years compared to 0% for those receiving initial larger field irradiation (P = 0.09). Fifteen patients recurred. All four patients who relapsed in the spine had received local radiotherapy and had elevated serum and CSF‐AFP at baseline. All three patients with ventricular relapse received local radiation therapy.ConclusionsNGGCT patients continue to relapse beyond 5 years. Late ventricular relapse occurred even in patients without clear evidence of germinoma component. Elevated CSF‐AFP at diagnosis is associated with poor DFS and risk for distant CNS relapse. Patients with residual radiographic disease after chemotherapy or residual malignant histologies after second‐look surgery have inferior outcomes. Our data support consideration of treatment intensification for these patients.

Abstract Background Despite advances in modern therapy, high-grade gliomas continue to portend a dismal prognosis and nearly all patients will experience relapse. Unfortunately, salvage options remain limited. In this study, we assessed outcomes for patients with recurrent gliomas treated with reirradiation. Methods We retrospectively identified 48 glioma patients treated with reirradiation between 2013 and 2016. All had radiographic or pathologic evidence of recurrence. Prognostic factors were abstracted from the electronic medical record. Results Initial surgery included biopsy in 15, subtotal resection in 21, and gross total resection in 12. Initial chemotherapy included temozolomide (TMZ) in 31, TMZ+dasatinib in 7, TMZ+vorinostat in 3, and procarbazine, lomustine, and vincristine in 2. The median dose of primary radiotherapy was 60 Gy delivered in 30 fractions. Median overall survival (OS) and progression-free survival (PFS) from initial diagnosis were 3.2 and 1.7 years, respectively. A total of 36 patients failed salvage bevacizumab before reirradiation. Salvage surgery was performed before reirradiation in 21 patients. Median time to reirradiation was 1.7 years. Median follow-up was 13.7 months from reirradiation. Concurrent systemic therapy was given in 33 patients (bevacizumab in 27, TMZ in 8, and lomustine in 2). Median PFS and OS after reirradiation were 3.2 and 6.3 months, respectively. Radionecrosis occurred in 4 patients and no radionecrosis was seen in patients receiving concurrent bevacizumab with reirradiation (0% vs 19%, P = .03). Conclusions Reirradiation may result in delayed tumor progression with acceptable toxicity. Prospective trials are needed to determine the impact of reirradiation on tumor progression and quality of life.

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.

126 Background: Inflammatory breast cancer (IBC) is an aggressive breast cancer variant, with 5-yr overall survival (OS) typically reported at 40-45%. We recently presented our results with once-daily radiotherapy (RT) as a component of trimodality therapy, with 5-yr OS of 64%. Herein we report patient and treatment factors associated with locoregional control (LRC). Methods: With permission of the IRB, review of medical records at the Mayo Clinic in Rochester, MN was performed to identify patients treated with RT for IBC from 2000-2010. Patients with non-metastatic, clinically diagnosed IBC were included. OS, LRC and distant metastasis-free survival (DMFS) were assessed using the Kaplan-Meier method. First recurrence in the chest wall or regional lymph nodes was defined as a locoregional recurrence (LRR). Results: 52 women were included in the analysis. Median age at diagnosis was 54 years (range 23-83). Median follow-up for the population was 3.6 years (range 0.7 – 11.9). All patients were treated with adjuvant RT to the chest wall and draining nodal basins in once-daily fractions of 1.8-2.25 Gy (median 2 Gy), to a median of 50 Gy (range 46-60 Gy). Actuarial 5-yr LRC was 85%. LRR was associated with poorer DMFS and OS (p < 0.01). Factors significantly associated with improved LRC included lack of extracapsular extension (ECE) and use of adjuvant chemotherapy (p < 0.05). Factors associated with a trend towards LRC included use of bolus, absence of boost, node negativity at time of surgery and pathologic complete response (pCR). Daily bolus was employed in 90% of patients and was most commonly (68%) 1 cm in thickness. There was a trend towards improved 5-yr LRC when bolus ≥ 1 cm was employed daily (93% v. 67%, p = 0.06). Patients who received a boost to the mastectomy scar (62% of the population, median of 10 Gy, range 10-16 Gy) had poorer LRC (78% v. 100%, p = 0.08), but superior 5-yr DMFS (78% v. 34%, p = 0.035) and OS (77% v. 34%, p = 0.04). Conclusions: LRC is associated with improved OS in IBC. Lack of ECE and use of adjuvant chemotherapy are associated with improved LRC in women with IBC. Node negativity, pCR and use of daily bolus ≥1 cm in thickness are associated with a trend towards improved LRC. The impact of boost requires further analysis.

AbstractBackgroundThe prognostic significance of having extraskeletal (EES) versus skeletal Ewing sarcoma (ES) in the setting of modern chemotherapy protocols is unknown. The purpose of this study was to compare the clinical characteristics, biologic features, and outcomes for patients with EES and skeletal ES.MethodsPatients had localized ES and were treated on two consecutive protocols using five‐drug chemotherapy (INT‐0154 and AEWS0031). Patients were analyzed based on having an extraskeletal (n = 213) or skeletal (n = 826) site of tumor origin. Event‐free survival (EFS) was estimated using the Kaplan–Meier method, compared using the log‐rank test, and modeled using Cox multivariate regression.ResultsPatients with extraskeletal ES (EES) were more likely to have axial tumors (72% vs. 55%; P < 0.001), less likely to have tumors >8 cm (9% vs. 17%; P < 0.01), and less likely to be white (81% vs. 87%; P < 0.001) compared to patients with skeletal ES. There was no difference in key genomic features (type of EWSR1 translocation, TP53 mutation, CDKN2A mutation/loss) between groups. After controlling for age, race, and primary site, EES was associated with superior EFS (hazard ratio = 0.69; 95% confidence interval: 0.50–0.95; P = 0.02). Among patients with EES, age ≥18, nonwhite race, and elevated baseline erythrocyte sedimentation rate were independently associated with inferior EFS.ConclusionClinical characteristics, but not key tumor genomic features, differ between EES and skeletal ES. Extraskeletal origin is a favorable prognostic factor, independent of age, race, and primary site.

OBJECT While extent of resection has been shown to correlate with outcomes after myxopapillary ependymoma (MPE) resection, the effect of capsular violation has not been well studied. The role of adjuvant radiation also remains controversial. In this paper the authors' goals were to evaluate outcomes following resection of MPE based on intraoperative capsular violation and to explore the role of adjuvant radiotherapy in cases of capsular violation. METHODS A retrospective review of patients undergoing resection of MPE at 2 academic institutions between 1990 and 2013 was performed. Cases with dissemination at presentation, less than 12 months of follow-up, or incomplete records were excluded. Extent of resection was defined as en bloc if all visible tumor was removed without capsular violation, gross-total resection (GTR) if all visible tumor was removed, but with capsular violation, and subtotal resection (STR) if a known residual was left at the time of surgery. Postoperative MR images were reviewed to confirm the extent of resection. Primary outcomes were progression-free survival (PFS) and overall recurrence rates. The effects of extent of resection, capsular violation, and adjuvant radiotherapy on recurrence rates and PFS were analyzed using Kaplan-Meier statistics. Associations between recurrence and preoperative variables were evaluated using Fisher exact methods and t-tests where appropriate. RESULTS Of the 107 patients reviewed, 58 patients (53% were male) met inclusion criteria. The mean age at surgery was 40.8 years (range 7–68 years). The median follow-up was 51.5 months (range 12–243 months). Extent of resection was defined as en bloc in 46.5% (n = 27), GTR in 34.5% (n = 20), and STR in 18.9% (n = 11). No recurrences were noted in the en bloc group, compared with 15% (n = 3) and 45% (n = 5) in the GTR and STR groups. En bloc resection was achieved most frequently in tumors involving the conus. Twelve patients (20%) underwent adjuvant radiotherapy following either STR or GTR. The overall recurrence rate was 13.8% (n = 8), and the 5-year PFS was 81%. Capsular violation was associated with a higher recurrence rate (p = 0.005). Adjuvant radiotherapy showed a nonsignificant trend of lower recurrence rates (16.7% vs 31.6%, p = 0.43) and longer PFS at 5 years (83.3% vs 49.9%, p = 0.16) in cases of capsular violation. CONCLUSIONS A strong correlation between capsular violation and recurrence was found following removal of MPE and should be assessed when defining extent of resection in future studies. Although the use of adjuvant radiotherapy in cases of capsular violation showed a trend toward improved PFS, further investigation is needed to establish its role as salvage therapy also appears to be effective at halting disease progression.

Background. Radiotherapy has been utilized for metastatic and recurrent osteosarcoma and Ewing sarcoma (ES), in order to provide palliation and possibly prolong overall or progression-free survival. Stereotactic body radiotherapy (SBRT) is convenient for patients and offers the possibility of increased efficacy. We report our early institutional experience using SBRT for recurrent and metastatic osteosarcoma and Ewing sarcoma.Methods. We reviewed all cases of osteosarcoma or ES treated with SBRT between 2008 and 2012.Results. We identified 14 patients with a total of 27 lesions from osteosarcoma(n=19)or ES(n=8). The median total curative/definitive SBRT dose delivered was 40 Gy in 5 fractions (range, 30–60 Gy in 3–10 fractions). The median total palliative SBRT dose delivered was 40 Gy in 5 fractions (range, 16–50 Gy in 1–10 fractions). Two grade 2 and 1 grade 3 late toxicities occurred, consisting of myonecrosis, avascular necrosis with pathologic fracture, and sacral plexopathy. Toxicity was seen in the settings of concurrent chemotherapy and reirradiation.Conclusions. This descriptive report suggests that SBRT may be a feasible local treatment option for patients with osteosarcoma and ES. However, significant toxicity can result, and thus systematic study is warranted to clarify efficacy and characterize long-term toxicity.