Stereotactic radiosurgery for melanoma brain metastases: Concurrent immune checkpoint inhibitor therapy associated with superior clinicoradiological response outcomes.

INTRODUCTION/PURPOSE: This study assessed long-term clinical and radiological outcomes following treatment with combination stereotactic radiosurgery (SRS) and immunotherapy (IT) for melanoma brain metastases (BM). METHODS: A retrospective review was performed in a contemporary cohort of patients with melanoma BM at a single tertiary institution receiving Gamma Knife® SRS for melanoma BM. Multivariate Cox proportional-hazards modelling was performed with a P <0.05 for significance. RESULTS: 101 patients (435 melanoma BM) were treated with SRS between January-2015 and June-2019. 68.3% of patients received IT within 4 weeks of SRS (concurrent) and 31.7% received SRS alone or non-concurrently with IT. Overall, BM local control rate was 87.1% after SRS. Median progression free survival was 8.7 months. Median follow-up was 29.2 months. On multivariate analysis (MVA), patients receiving concurrent SRS-IT maintained a higher chance of achieving a complete (CR) or partial response (PR) [HR 2.6 (95% CI: 1.2-5.5, P = 0.012)] and a reduced likelihood of progression of disease (PD) [HR 0.52 (95% CI: 0.16-0.60), P = 0.048]. Any increase in BM volume on the initial MRI 3 months after SRS predicted a lower likelihood of achieving long-term CR or PR on MVA accounting for concurrent IT, BRAF status and dexamethasone use [HR = 0.048 (95% CI: 0.007-0.345, P = 0.0026)]. Stratified volumetric change demonstrated a sequential relationship with outcomes on Kaplan-Meier analysis. CONCLUSION: Concurrent SRS-IT has favourable clinical and radiological outcomes with respect to CR, PR and a reduced likelihood of PD. Changes in BM volume on the initial MRI 3 months after SRS were predictive of long-term outcomes for treatment response.

Evidence of dose-response following hypofractionated stereotactic radiotherapy to the cavity after surgery for brain metastases.

BACKGROUND AND OBJECTIVE: A retrospective review of consecutive patients between January 2012 and December 2018 receiving hypofractionated stereotactic radiotherapy (HSRT) to the cavity after resection for brain metastases was performed. METHODS: Treatment was delivered using an appropriately commissioned linear accelerator. The primary outcome was time to radiological or histological confirmation of local recurrence following completion of HSRT. Dose-fractionation regimens were converted to biologically 2 Gy-equivalent doses assuming α/ß = 10 (EQD2[10]). Multivariate Cox proportional hazards modelling was performed to determine hazard ratios (HR) with respective 95% confidence intervals (CI). The Log-rank test was used to determine p values taking statistical significance p < 0.05. RESULTS: There were 134 patients and 144 cavities identified. The most common primary histologies were melanoma (n = 49) and lung (n = 32). 116 patients (87%) underwent a gross total resection. Median planning target volume (PTV) was 28 cm3 (range 2.4-149.2). Median EQD2[10] was 38.4 Gy (range 22.3-59.7) and 24 Gy in 3 fractions was the most common regimen. 12 (9%) patients demonstrated local recurrence at median interval 215 days (range 4-594). 7 (5%) patients experienced grade 3 or higher toxicities. In multivariate analysis, EQD2[10] was associated with local failure such that increased equivalent doses improved local control [HR = 0.79 and 95% CI 0.65-0.96, p = 0.0192]. There were no significant associations for primary histology, patient age, volume of residual disease, PTV volume or location. CONCLUSION: This large series demonstrates that HSFRT to the surgical resection cavity for brain metastases has improved local control with increasing dose. Rates of grade 3 or higher toxicity were low overall.

Incidence and risk factors of advanced neoplasia after endoscopic mucosal resection of colonic laterally spreading lesions.

PURPOSE: To investigate advanced neoplasia (AN) after endoscopic mucosal resection (EMR) of colonic laterally spreading lesions (LSLs). METHODS: A retrospective study of patients who underwent injection-assisted EMR of colonic LSLs ≥ 10 mm was performed. Primary outcome was overall rate of AN at initial surveillance colonoscopy. Secondary outcomes were the rates of residual AN (rAN) at the EMR site and metachronous AN (mAN), and analysis of risk factors for AN, including effect of surveillance guidance. RESULTS: Three hundred seventy-four patients underwent successful EMR for 388 LSLs. AN occurred in 66/374 (17.6%) patients on initial surveillance colonoscopy at median follow-up of 364.5 days. Two patients had both rAN and mAN, for a total of 68 instances of AN, including 30/374 (8.0%) cases of rAN and 38/374 (10.2%) cases of mAN. On multivariate analysis, use of piecemeal resection was associated with increased likelihood of residual AN (P = 0.003, OR 9.2, 95% CI 2.1-33.3). Twenty-nine out of thirty cases (96.7%) of rAN were successfully endoscopically managed at surveillance colonoscopy. CONCLUSIONS: AN occurred in 17.6% of all patients at initial surveillance colonoscopy at a median of 1 year after EMR. Roughly half of the instances of AN were metachronous lesions. Our data support a 1-year surveillance interval after EMR of LSLs ≥ 10 mm with careful inspection of the entire colon, not just the prior resection site.

En bloc endoscopic mucosal resection is equally effective for sessile serrated polyps and conventional adenomas.

BACKGROUND: Sessile serrated polyps (SSPs) are associated with higher rates of incomplete resection compared to conventional adenomas after traditional snare polypectomy. Outcomes after endoscopic mucosal resection (EMR) are less established. The aim of this study was to evaluate the rate of residual neoplasia at surveillance colonoscopy for SSPs compared to conventional adenomas ≥ 10 mm after en bloc EMR. METHODS: Retrospective cohort study of consecutive patients referred for EMR of a colonic lesion ≥ 10 mm from 2005 to 2013. Data on procedures, histopathology, and surveillance colonoscopies were recorded. The primary outcome was rate of macroscopically evident residual neoplasia at surveillance colonoscopy for SSPs compared to adenomas. Secondary outcomes included rate of neoplasia at the resection margin. RESULTS: 283 consecutive patients with 293 polyps underwent en bloc EMR including 101 SSPs and 192 adenomas. Pathology commented on the lateral resection margins of the specimen in 235 cases (80%). Of these, neoplasia was noted at the resection margin in 29/64 SSPs (45.3%) compared to 65/171 adenomas (38.0%; P = .37). Surveillance data were available for 153 index lesions with a median interval of 13 months (interquartile range, 10.75-23.25 months). Ten resection sites (6.5%) were found to have residual neoplasia, including 2/52 SSPs (3.8%) and 8/101 adenomas (7.9%; P = .50). Of the cases with surveillance data 128/153 (84%) commented on the lateral margin of the resection specimen. Residual neoplasia was noted in 3/68 lesions (4.4%) with negative margins compared to 5/60 lesions (8.3%) with positive margins (P = .47). CONCLUSIONS: En bloc EMR for colonic lesions ≥ 10 mm is associated with a 6.5% rate of macroscopic residual neoplasia. Although 45% of SSPs had neoplasia extending to the resection margin, rates of residual neoplasia at surveillance colonoscopy were low. These results suggest that when feasible en bloc EMR is a reasonable option to resect SSPs ≥ 10 mm.