No Acute Changes in LVEF Observed With Concurrent Trastuzumab and Breast Radiation With Low Heart Doses.

INTRODUCTION/BACKGROUND: Treatment for HER2-postitive breast cancer often includes trastuzumab, breast/chest wall (CW) radiation (RT), and anthracyclines, all of which have cardiac toxicity. We aimed to evaluate the relationship between heart dose and acute left ventricular ejection fraction (LVEF) changes in patients who received concurrent trastuzumab and breast/CW RT with and without anthracycline use. PATIENTS AND METHODS: We retrospectively reviewed all nonmetastatic breast cancer patients from 2008 to 2015 who received concurrent trastuzumab and breast/CW RT. Baseline LVEF was compared with the LVEF closest to treatment completion as well as with the lowest post-treatment LVEF. LVEF changes were correlated with laterality, heart dosimetric parameters, and doxorubicin use. RESULTS: Eighty-eight patients were included in our analysis. The median follow-up was 45 months. Forty-one patients were right-sided and 47 left-sided. Thirty-one patients received doxorubicin, 16 right-sided and 15 left-sided. Mean heart dose was 1.10 Gy and 3.63 Gy for right- and left-sided patients, respectively (P < .001). In the entire cohort, a significant LVEF decrease of 3.0% was observed pre- and post-treatment. There was a significant effect of doxorubicin (P = .013) and a nonsignificant effect of RT laterality (P = .088) on LVEF change. The test of interaction between doxorubicin and laterality was not significant (P = .90). No significant association was found between LVEF change and heart dosimetric parameters, including percent volume of heart receiving 5 Gy (V5), 10 Gy (V10), 20 Gy (V20), and 45 Gy (V45), and maximum dose. Similar results were found when baseline LVEF was compared with the lowest post-treatment LVEF. CONCLUSION: With cardiac doses < 4 Gy, declines in LVEF were not related to tumor laterality or heart dosimetric parameters. Statistically significant LVEF decreases were mainly attributed to doxorubicin.

Anatomic tumor location influences the success of contemporary limb-sparing surgery and radiation among adults with soft tissue sarcomas of the extremities.

PURPOSE: To examine the influence of anatomic location in the upper extremity (UE) vs. lower extremity (LE) on the presentation and outcomes of adult soft tissue sarcomas (STS). METHODS AND MATERIALS: From 2001 to 2008, 118 patients underwent limb-sparing surgery (LSS) and external beam radiotherapy (RT) with curative intent for nonrecurrent extremity STS. RT was delivered preoperatively in 96 and postoperatively in 22 patients. Lesions arose in the UE in 28 and in the LE in 90 patients. Patients with UE lesions had smaller tumors (4.5 vs. 9.0 cm, p < 0.01), were more likely to undergo a prior excision (43 vs. 22%, p = 0.03), to have close or positive margins after resection (71 vs. 49%, p = 0.04), and to undergo postoperative RT (32 vs. 14%, p = 0.04). RESULTS: Five-year actuarial local recurrence-free and distant metastasis-free survival rates for the entire group were 85 and 74%, with no difference observed between the UE and LE cohorts. Five-year actuarial probability of wound reoperation rates were 4 vs. 29% (p < 0.01) in the UE and LE respectively. Thigh lesions accounted for 84% of the required wound reoperations. The distribution of tumors within the anterior, medial, and posterior thigh compartments was 51%, 26%, and 23%. Subset analysis by compartment showed no difference in the probability of wound reoperation between the anterior and medial/posterior compartments (29 vs. 30%, p = 0.68). Neurolysis was performed during resection in (15%, 5%, and 67%, p < 0.01) of tumors in the anterior, medial, and posterior compartments. CONCLUSIONS: Tumors in the UE and LE differ significantly with respect to size and management details. The anatomy of the UE poses technical impediments to an R0 resection. Thigh tumors are associated with higher wound reoperation rates. Tumor resection in the posterior thigh compartment is more likely to result in nerve injury. A better understanding of the inherent differences between tumors in various extremity sites will assist in individualizing treatment.

Radiation therapy alone for imaging-defined meningiomas.

PURPOSE: To assess local control and treatment-related toxicity of single-modality radiation therapy (RT) in the treatment of imaging-defined meningiomas. METHODS AND MATERIALS: The records of Emory University School of Medicine, Atlanta, GA, were reviewed between 1985 and 2003. We identified 41 patients with 42 meningiomas treated with RT alone for lesions diagnosed on imaging alone. No patients received a histologic diagnosis. Patients in whom there was uniform agreement that the tumor represented a meningioma were accepted for therapy. Of the patients, 22 were treated with stereotactic radiosurgery (SRS), 11 with fractionated stereotactic radiotherapy (FSR), and 9 with three-dimensional conformal therapy (3DCRT). The median doses of SRS, FSR, and 3DCRT were 14 Gy, 50.4 Gy, and 52.2 Gy, respectively. RESULTS: Median follow-up was 60 months. Of 42 meningiomas, 39 were locally controlled. The 8-year actuarial local control rate by Kaplan-Meier methods was 94%. One failure occurred 6 months after 3DCRT, a second at 34 months after FSR, and a third at 125 months after SRS. A temporary symptomatic radiation-related neurologic sequela developed in 1 patient treated with SRS. No fatal treatment complications occurred. The 8-year rate for actuarial freedom from complication survival by Kaplan-Meier methods was 97%. CONCLUSIONS: RT alone is an attractive alternative to surgery for imaging-defined meningiomas without significant mass effect. It offers local control comparable to surgical resection with minimal morbidity. RT should be considered as a viable alternative to surgery for tumors in various locations.

Incidence, risks, and sequelae of posterior fossa syndrome in pediatric medulloblastoma.

PURPOSE: To investigate the incidence, risks, severity, and sequelae of posterior fossa syndrome (PFS) in children with medulloblastoma. METHODS AND MATERIALS: Between 1990 and 2007, 63 children with medulloblastoma at Emory University and Children's Healthcare of Atlanta were treated with craniectomy followed by radiation. Fifty-one patients were assigned to a standard-risk group, and 12 patients were assigned to a high-risk group. Five patients had <1.5-cm(2) residual tumor, 4 had >or=1.5-cm(2) residual tumor, and the remainder had no residual tumor. Eleven patients had disseminated disease. Patients received craniospinal irradiation at a typical dose of 23.4 Gy or 36 Gy for standard- or high-risk disease, respectively. The posterior fossa was given a total dose of 54 or 55.8 Gy. Nearly all patients received chemotherapy following cooperative group protocols. RESULTS: Median follow-up was 7 years. PFS developed in 18 patients (29%). On univariate analysis, brainstem invasion, midline tumor location, younger age, and the absence of radiographic residual tumor were found to be predictors of PFS; the last two variables remained significant on multivariate analysis. From 1990 to 2000 and from 2001 to 2007, the proportions of patients with no radiographic residual tumor were 77% and 94%, respectively. During the same eras, the proportions of patients with PFS were 17% and 39%. Only 4 patients had complete recovery at last follow-up. CONCLUSIONS: The incidence of PFS increased in the latter study period and is proportional to more aggressive surgery. Children with midline tumors exhibiting brainstem invasion are at increased risk. With the increased incidence of PFS and the permanent morbidity in many patients, the risks and benefits of complete tumor removal in all patients need to be reexamined.