Routman, David M.

Abstract PURPOSE To compare outcomes of adults with high-risk grade II oligodendroglioma treated with adjuvant radiotherapy plus adjunctive TMZ versus PCV. METHODS We queried a multi-institutional database from the Cleveland Clinic and Mayo Clinic of 158 adults with WHO grade II glioma who were high-risk (age > 40 and/or subtotal-resection [STR]) and underwent adjuvant chemoradiation (TMZ or PCV) between 1997–2017. We included patients with oligodendroglioma by 1p/19q-codeletion or traditional histopathology. Fisher’s exact test was used to associate factors with chemotherapy group. The log-rank test was used to compare OS and PFS by chemotherapy group and clinical characteristics. RESULTS 52 patients were included with a median follow-up of 44 months (range, 3–259). Median age was 44 (range, 22–73), 49 (94%) underwent STR, and 28 (54%) were male. Presenting symptoms were seizure in 35 (67%) patients, sensory in 14 (27%), and motor in 8 (15%). Oligodendroglioma classification was by 1p/19q-codeletion in 27 (52%) and traditional histopathology in 25 (48%) patients. Median radiation dose was 54 Gy (range, 45–60). Chemotherapy was TMZ in 34 (65%) patients and PCV in 18 (35%). Patients who were older (P=0.003), lacked seizures (P=0.03), or had motor symptoms (P=0.04) were more likely to receive TMZ. Median OS was 223 months (95% CI, 181-not estimable) and median PFS was 118 months (95% CI, 69–223). Treatment with TMZ versus PCV was not associated with OS (median 186 vs. 223 months, respectively; P=0.71) or PFS (median 110 vs. 131 months, respectively; P=0.19). Age >40 (P=0.009) and motor symptoms (P=0.027) were associated with adverse OS. Presence of motor symptoms was associated with worse PFS (P=0.008). CONCLUSION There was no statistically significant difference in OS or PFS between adjunctive TMZ versus PCV for adult high-risk grade II oligodendroglioma. A larger cohort with longer follow-up will provide additional insight.

Abstract PURPOSE: Preoperative stereotactic radiosurgery (SRS) for symptomatic brain metastases has arisen as a therapeutic option for patients with brain lesions, potentially reducing radionecrosis risk, leptomeningeal disease risk, as well as delays in systemic therapy after craniotomy. The purpose of our work is to analyze the current evidence regarding 1-year local control (LC) and RN rates in the preoperative and postoperative settings. METHODS AND MATERIALS: Population, Intervention, Control, Outcomes, Study Design/Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology guidelines were used to select articles in which patients had “large” brain metastases (>4 cm3 or >2 cm in diameter) solely treated with preoperative or postoperative SRS and 1-year LC and/or rates of RN reported. Radiosurgery was stratified by timing: preoperatively or postoperatively. Random effects meta-analyses using timing of SRS relative to surgery as covariates were conducted. Meta-regression and Wald-type tests were used to determine the effect of increasing tumor size on the summary estimate, where the null hypothesis was rejected for p < 0.05. RESULTS: Fifteen studies were included (of 314 screened), published between 2012 and 2018 with 854 brain metastases. Preoperative SRS was delivered in 229 lesions. The 1-year LC random effects estimate was 79.1% (95% confidence interval [CI]: 55.9–95.0%; I 2 = 80%) for preoperative SRS and 80.5% (95% CI: 66.3–91.5%; I 2 = 93%) for postoperative SRS (p=0.9). Radionecrosis incidence random effects estimate was 2.1% (95% CI: 0.1–8.6%; I 2 = 36%) for preoperative SRS and 6.3% (95% CI: 1.1–15.4%; I 2 = 90%) for postoperative SRS (p=0.52). CONCLUSIONS: Rates of 1-year LC and RN incidence are similar after preoperative SRS as compared to postoperative SRS for large brain metastases. Results from ongoing prospective clinical trials studying preoperative SRS are important to further investigate these two techniques.

147 Background: Lymphopenia during radiation therapy (RT) has been associated with worse oncologic outcomes in a number of malignancies, including esophageal cancer (EC). No studies to date have investigated specific dosimetric parameters associated with this lymphopenia in EC. We performed an analysis of RT dose to multiple organs at risk (OARs) to investigate associations with grade 4 lymphopenia (G4L). Methods: Consecutive EC patients receiving curative intent chemoradiotherapy +/- surgery between July of 2015 and December of 2017 were included. Lymphocyte nadir was defined as the lowest lymphocyte count during RT. G4L was defined as absolute lymphocyte count <200/mm3. Dose to OARs including aorta, body, bone marrow, heart, liver, lung, and spleen were calculated. Univariate logistic regression analyses were performed for each OAR at the 1, 5, 10, 15, 20, 30, 35, 40, and 50 Gy levels with volume receiving dose ‘x’(VxGy) analyzed as a continuous variable per 10% increase. Clinical tumor volume (CTV) and RT modality (photon vs. proton) as well clinical factors including sex, stage (I/II vs. III/IV), age (per 10 year increase), and BMI (per 5 unit increase) were also analyzed. Results: One hundred forty-four pts were identified for inclusion. Seventy-nine pts received photon RT and 65 proton RT. Chemotherapy was weekly carbotaxol (99%). G4L at nadir was 40% overall (56% photon, 22% proton). By organ, body V1-V30Gy (OR 1.45-8.18, p<0.01), heart V1-V30Gy (OR 1.24-1.49, p<0.01), liver V1-V35Gy (OR 1.23-2.75, p<0.01), lung V1-V30Gy (OR 1.26-5.73 p<0.01), and spleen V1-V40Gy (OR 1.26-1.49 p<0.01) were highly associated with G4L whereas dose to aorta and bone marrow were not. Advanced stage (OR, 3.92 p<0.01), photon vs. proton (OR 4.58 p<0.01), and CTV (per 100 cc’s (OR=1.21, p<0.01)) were also associated with G4L. Sex, age, and BMI were not associated with G4L. Conclusions: Low to intermediate dose volumes to OARs including body, spleen, liver, lungs, and heart were associated with G4L. These findings provide rational for the differences seen in rates of G4L for photon versus proton RT.

Abstract Stereotactic Radiosurgery ( SRS ) is considered standard of care for patients with 1–3 brain metastases ( BM ). Recent observational studies have shown equivalent OS in patients with 5+ BM compared to those with 2–4, suggesting SRS alone may be appropriate in these patients. We aim to review outcomes of patients treated with SRS with 2–4 versus 5+ BM . This analysis included consecutive patients from 1994 to 2015 treated with SRS . Of 1017 patients, we excluded patients with a single BM and patients without adequate survival data, resulting in 391 patients. All risk factors were entered into univariate analysis using Cox proportional hazards model, and significant factors were entered into multivariate analysis ( MVA ). We additionally analyzed outcomes after excluding patients with prior surgery or whole‐brain radiotherapy ( WBRT ). Median follow‐up was 7.1 months. Median KPS was 90, mean age was 59, and most common histologies were melanoma and lung. Median tumor volume was 3.41 cc. Patients with 2–4 BM had a median OS of 8.1 months compared to 6.2 months for those with 5+ BM ( P = 0.0136). On MVA , tumor volume, KPS , and histology remained significant for OS , whereas lesion number did not. Similar results were found when excluding patients with prior surgery or WBRT . Rather than lesion number, the strongest prognostic factors for patients undergoing SRS were tumor volume >10 cc, KPS , and histology. BM number may therefore not be the most important criterion for candidacy for SRS . Patients with 5 or more BM should be considered for SRS .