Laack, Nadia

Abstract BACKGROUND CNS ependymal tumors rarely demonstrate mixed subependymal and ependymal pathology. The clinical course of these tumors is difficult to predict, but prior studies have identified TERT mutations and loss of chromosome 6 as poor prognostic factors in these tumors when located in the posterior fossa. METHODS In this retrospective single-institution study, patients with a diagnosis of mixed subependymoma/ependymoma were identified and chart reviewed to describe demographics, pathological findings, treatment courses and clinical outcomes. RESULTS Eleven patients (median age 57, 2 female, 9 male) were identified. Ten tumors were in the posterior fossa and 1 in the cervical spine. At diagnosis, 2 underwent gross total resection, 8 underwent subtotal resection, and 1 was only biopsied. Radiotherapy was administered to 5 patients at initial diagnosis (54Gy in 30 fractions). Systemic therapy (temozolomide and bevacizumab) was administered at recurrence to 2 patients. Loss of chromosome 6 was present in 5 /11 patients and TERT mutations were present in 4/11 patients, with both present in 3/11 patients. Median progression-free survival (mPFS) was 90.1 months (95% CI: 90.1–NA), with 3 progression events observed at 22, 90, and 107 months. Median follow-up duration was 27.9 months. Receiving radiotherapy had a longer mPFS (98 vs 22 months, p=0.15), although non-significant. At the time of data cut-off none of the patients were deceased. CONCLUSIONS Mixed subependymoma/ependymoma is a rare diagnosis with varying clinical outcomes. Our case series demonstrated that the majority of patients did not exhibit the previously identified poor prognostic factors. Although non-significant due to limited case numbers, radiotherapy was suggestive of longer mPFS.

Abstract Medulloblastoma is a posterior fossa tumor rarely diagnosed in adults. Treatment includes craniospinal irradiation (CSI). Proton CSI is increasingly utilized to decrease radiation dose to normal tissues, despite the lack of randomized data demonstrating decreased toxicity compared to photon CSI. This single institution retrospective study of 39 adult medulloblastoma patients includes nineteen patients treated with photon CSI prior to 2015, and twenty treated with proton CSI thereafter. Median age was 28 years (range 18-66). Molecular subtype was most commonly sonic hedgehog (68%). The most common fractionation schedule was 36 Gy CSI in 20 fractions (85% of photon and 58% of proton patients) with a boost to 54-55.8 Gy (92%). Proton CSI delivered significantly lower mean doses to the cochleae (median 32 Gy vs. 44 Gy), lacrimal glands (8 vs. 36 Gy), lens (2 vs. 28 Gy), parotid glands (3 vs. 26 Gy), pharyngeal constrictors (6 vs. 15 Gy), esophagus (2 vs. 29 Gy), heart (0 vs. 14 Gy), lungs (1 vs. 7 Gy), liver (0.1 vs. 7 Gy), and skin (38 vs. 51 Gy) (all p< 0.001). Patients receiving proton CSI had significantly lower rates of acute dysphagia of any grade (5% vs. 35%, p= 0.044) and decreased median weight loss during radiation (+1.0 vs. -2.8 kg, p= 0.011). Acute hospitalization was associated with increased weight loss (p= 0.009). Median follow-up was 2.9 and 12.9 years for proton and photon patients, respectively, limiting late toxicity and outcome comparisons. At last follow-up five photon patients had died (two of progressive disease, three without recurrence ages 41-63) and 21% had experienced major cardiovascular events. At 10 years, 89% were alive and 82% were recurrence free. In conclusion, this study demonstrates dosimetric improvements with proton CSI, potentially leading to decreased acute toxicity including dysphagia and weight loss during treatment.

Abstract Background Proton beam therapy (PBT) is a promising radiotherapeutic method by which the proton Bragg peak may be exploited to reduce the dose to non-target normal tissues, when compared with the conventional photon treatment (PhT). Purpose To evaluate the mechanical function of the left ventricle by endocardial longitudinal (GLS-basic strain), circumferential (GCS) and radial strain (GRS) and systolic (SRs) and early diastolic (SRe) strain rate following thoracic radiotherapy. Methods Between March 2016 and March 2017, 58 patients with breast or thoracic cancer scheduled to receive radiotherapy were enrolled prospectively and, underwent 2D-STE echocardiography with basic (GLS) and comprehensive (GCS, GRS,GLSRs, GCSRs, GRSRs, GLSRe, GCSRe, GRSRe parameters) analysis at pre-treatment, mid-treatment, end of treatment, 3 month and 1 year follow-up. LVEF was calculated by the biplane Simpson technique. Shapiro-Wilk's test was performed to evaluate the normal distribution of the data. Comparison between groups was performed with Student's t-test or Wilcoxon test for quantitative variables and with Chi-Square test or Fisher's exact test for qualitative variables. Tukey-Kramer method was used to compare means during follow up. A p-value <0.05 was assumed as the level of statistical significance. Results Mean age was 53.3±10.9 years and 91.3% were women. PBT was used to treat 38 patients; PhT in 20. The median of the mean heart dose was lower with PBT than PhT (79±92 vs 829±1121 cGy, respectively [P<.001]). No significant changes in LVEF or GLS for PBT or PhT were seen. Comprehensive strain analysis showed changes in endocardial longitudinal, radial, and circumferential early diastolic strain rate (SRe) in patients undergoing photon beam (PhT) up to one year of follow up (Table 1). No changes were detected in the PBT group. All other variables were non-significant (Not shown). Conclusion This is the first longitudinal study, with a one-year follow-up, that shows the relaxation properties of LV are compromised during PhT but not PBT. These findings should be followed in time to evaluate their influence on overall heart function. Funding Acknowledgement Type of funding sources: None. Table 1

Abstract Introduction Coronary artery calcification (CAC) is associated with and identifies patients at higher risk of major adverse cardiovascular events (MACE). However, the prevalence, characteristics, and outcomes of cancer patients with CAC on CT before or after chest radiation therapy (RT) are not well addressed. Methods Retrospective cohort study of all breast cancer patients who underwent chest RT at Mayo Clinic Rochester in 2010. All pre-RT CTs were reviewed and the extent of CAC was recorded in addition to history of pre-RT atherosclerotic risk factors (hypertension (HTN), diabetes mellitus (DM), dyslipidemia, and smoking), history of pre-RT cardiovascular disease (CVD), and RT dosage. MACE (sudden cardiac death (SCD), acute coronary syndrome (ACS), and stroke), and CAC progression in follow-up were recorded. CAC extent was quantified before and on 5-year follow-up CT scan in all patients, and a positive change was considered progression. Patients were divided into 2 groups based on the presence of CAC before RT: present (group 1) or absent (group 2). Results Our cohort was comprised of 244 breast cancer patients who received chest RT. A total of 39 patients (16.9%) had evidence of CAC on CT prior to RT. Compared with patients without CAC before RT (n=205), those with CAC before RT were found to be older (71.8±7.7 vs 58.9±11.3, p<0.01), had higher pre-RT history of HTN (84.6% vs 47.8%); p<0.01), DM (20.5% vs 4.4%; p<0.01), dyslipidemia (74.2% vs 40%; p<0.01), CAD (23.1% vs 3.9%; p<0.01), and stroke (7.69% vs 1.45%; p=0.04). Following RT, patients in group 1 were more likely to exhibit ACS (33.3% vs 2.9%; p<0.01), and stroke (22.6% vs 5.2%; p<0.01). Multinomial logistic regression identified pre-RT CAD pre-RT CAC (β=1.01 (0.33–1.69), OR=7.60 (1.93–29.93); p=0.02) pre-RT CAD (β=0.78 (0.06–1.49), OR=4.74 (1.14–19.74); p=0.03) as independent predictors for the development of MACE after RT. Progression in CAC after RT was found in 61.9% of all patients (13/21) who developed MACE. Conclusion MACE in breast cancer patients undergoing RT can be predicted before RT based on the CV risk factor and disease profile. The strongest predictor for MACE, however, is evidence of CAC before RT. These data provide a unique window for the identification and follow-up of breast cancer RT patients who have a risk of MACE. Funding Acknowledgement Type of funding source: None