Yttrium-90 Radiation Segmentectomy in Oligometastatic Secondary Hepatic Malignancies.

PURPOSE: To evaluate the safety and efficacy of yttrium-90 (90Y) radiation segmentectomy (RS) in the treatment of oligometastatic secondary hepatic malignancies. MATERIALS AND METHODS: This institutional review board-approved retrospective study evaluated 16 patients with oligometastatic secondary hepatic malignancies who were treated with RS. The median patient age was 61.9 years (range, 38.6-85.7 years). Of the 16 patients, 11 (68.8%) presented with solitary lesions. The median index tumor size was 3.1 cm (95% CI, 2.3-3.9). Primary outcomes were evaluation of clinical and biochemical toxicities using National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0, and imaging response using Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary outcomes were time to progression (TTP) and overall survival (OS) as estimated by the Kaplan-Meier method. RESULTS: Clinical Grade 3 toxicities were limited to 1 (6.7%) patient who experienced fatigue, abdominal pain, nausea, and vomiting. Biochemical Grade 3 toxicities occurred in 1 (6.7%) patient who experienced lymphopenia. No Grade 4 clinical or biochemical toxicities were identified. Disease control was achieved in 14 (93.3%) of 15 patients. The median TTP of the treated tumor was 72.9 months (95% CI, 11.2 to no estimate). The median OS was 60.9 months (95% CI, 24.7 to no estimate). CONCLUSIONS: 90Y RS displayed an excellent safety profile and was effective in achieving a high disease control rate in the treatment of oligometastatic secondary hepatic malignancies.

Long-term outcomes of spinal ependymomas: an institutional experience of more than 60 cases.

PURPOSE: Spinal ependymomas represent the most common primary intramedullary tumors for which optimal management remains undefined. When possible, gross total resection (GTR) is often the mainstay of treatment, with consideration of radiotherapy (RT) in cases of residual or recurrent tumor. The impact of extent of resection and radiotherapy remain understudied. OBJECTIVE: Report on a large institutional cohort with lengthy follow-up to provide information on long-term outcomes and to contribute to limited data assessing the value of extent of resection and RT. METHODS: Patients with pathologically proven primary spinal ependymoma between 1990 and 2018 were identified. Kaplan-Meier estimates were used to calculate progression-free survival (PFS); local-control (LC) and overall survival (OS). Logistic regression was used to analyze variables' association with receipt of RT. RESULTS: We identified 69 patients with ependymoma of which 4 had leptomeningeal dissemination at diagnosis and were excluded. Of the remaining cohort (n = 65), 42 patients (65%) had Grade II spinal ependymoma, 20 (31%) had Grade I myxopapillary ependymoma and 3 (5%) had Grade III anaplastic ependymoma; 54% underwent GTR and 39% underwent RT. With a median follow-up of 5.7 years, GTR was associated with improved PFS. For grade II lesions, STR+RT yielded better outcomes than STR alone (10y PFS 77.1% vs 68.2%, LC 85.7% vs 50%). Degree of resection was the only significant predictor of adjuvant radiotherapy (p < 0.0001). CONCLUSION: Our findings confirm the importance of GTR in spinal ependymomas. Adjuvant RT should be utilized in the setting of a subtotal resection with expectation of improved disease-related outcomes.

Mean Brain Dose Remains Uninfluenced by the Lesion Number for Gamma Knife Stereotactic Radiosurgery for 10+ Metastases.

OBJECTIVE: Gamma Knife (GK) stereotactic radiosurgery (SRS) is increasingly used as an initial treatment for patients with 10 or more brain metastases. However, the clinical and dosimetric consequences of this practice are not well established. METHODS: We performed a single-institution, retrospective analysis of 30 patients who received Gamma Knife SRS for 10 or more brain metastases in 1 session. We utilized MIM Software to contour the whole brain and accumulated the doses from all treated lesions to determine the mean dose delivered to the whole brain. Patient outcomes were determined from chart review. RESULTS: Our cohort had a median number of 13 treated lesions (range 10-26 lesions) for a total of 427 treated lesions. The mean dose to the whole brain was determined to be 1.8 ± 0.91 Gy (range 0.70-3.8 Gy). The mean dose to the whole brain did not correlate with the number of treated lesions (Pearson r = 0.23, P = 0.21), but was closely associated with tumor volume (Pearson r = 0.95, P < 0.0001). There were no significant correlations between overall survival and number of lesions or aggregate tumor volume. Fourteen patients (47%) underwent additional SRS sessions and 6 patients (20%) underwent whole-brain radiotherapy with a median of 6.6 months (range 3.0-50 months) after SRS. Two patients (6.6%) developed grade 2 radionecrosis following SRS beyond earlier whole-brain radiotherapy. CONCLUSION: The mean dose to the whole brain in patients treated with Gamma Knife SRS for 10 or more brain metastases remained low with an acceptable rate of radionecrosis. This strategy allowed the majority of patients to avoid subsequent whole-brain radiotherapy.

Implications of pneumonitis after chemoradiation and durvalumab for locally advanced non-small cell lung cancer.

BACKGROUND: Consolidation durvalumab improved overall survival (OS) in locally advanced non-small cell lung cancer (LA-NSCLC) treated with chemoradiotherapy (CRT) in the PACIFIC trial; however, pneumonitis was increased with durvalumab. We sought to examine real-world outcomes with the PACIFIC paradigm, especially factors associated with pneumonitis, using a multi-institutional review. METHODS: Patients with LA-NSCLC treated with CRT followed by durvalumab from January 2017-February 2019 were identified at 2 institutions. We characterized demographics, tumor factors, radiotherapy, and duration of durvalumab. We examined pneumonitis outcomes including re-challenge success, with secondary endpoints of progression-free survival (PFS) and OS. RESULTS: Thirty-four patients were included with median follow-up of 12 months (range, 3 to 20 months); 94% had stage III disease. The cumulative grade >2 pneumonitis rate was 26.5% with 2 patients developing grade 3 pneumonitis and no grade 4/5 events. Median time to pneumonitis after RT was 2.4 months (range, 0 to 4.9 months). Pneumonitis management included median prednisone dose of 60 mg for median taper of 6 weeks with durvalumab held for median of 4.5 weeks (range, 2 to 8 weeks); 70% of pneumonitis patients received durvalumab re-challenge, with pneumonitis recurring in 14% of patients. 3-month and 6-month pneumonitis-free-survival were 76.9% and 73.6%, respectively; 9- and 12-month OS were 96% (75.1-99.8%), 86.6% (63.5-95.5%), respectively; 9- and 12-month PFS were 68% (47.5-82.5%), 48.7% (25.3-68.3%). Pneumonitis development did not significantly impact PFS or OS (P>0.05). CONCLUSIONS: Among LA-NSCLC patients treated with CRT followed by consolidation durvalumab, more than 25% developed symptomatic pneumonitis. In this small case series, pneumonitis did not appear to negatively impact survival, and durvalumab re-challenge appeared feasible after pneumonitis treatment with steroids.

Commentary: preclinical efficacy of immune-checkpoint monotherapy does not recapitulate corresponding biomarkers-based clinical predictions in glioblastoma by Garg et al. (2017).

Preclinical modeling and gene expression analyses have yielded distinct observations for the role of immune checkpoint, IDO1, in glioblastoma (GBM). Accordingly, our recent work differs with Garg et al. (2017) with respect to IDO1 among preclinical and bioinformatic GBM datasets. Here, we discuss the methodological differences that affected study interpretation, and potentially, future clinical decision-making for IDO1-targeting approaches against GBM.