Robert H. Press

Comparing Preoperative With Postoperative Stereotactic Radiosurgery for Resectable Brain Metastases: A Multi-institutional Analysis.

BACKGROUNDnStereotactic radiosurgery (SRS) is an increasingly common modality used with surgery for resectable brain metastases (BM).nnnOBJECTIVEnTo present a multi-institutional retrospective comparison of outcomes and toxicities of preoperative SRS (Pre-SRS) and postoperative SRS (Post-SRS).nnnMETHODSnWe reviewed the records of patients who underwent resection of BM and either Pre-SRS or Post-SRS alone between 2005 and 2013 at 2 institutions. Pre-SRS used a dose-reduction strategy based on tumor size, with planned resection within 48 hours. Cumulative incidence with competing risks was used to determine estimated rates.nnnRESULTSnA total of 180 patients underwent surgical resection for 189 BM: 66 (36.7%) underwent Pre-SRS and 114 (63.3%) underwent Post-SRS. Baseline patient characteristics were balanced except for higher rates of performance status 0 (62.1% vs 28.9%, P < .001) and primary breast cancer (27.2% vs 10.5%, P = .010) for Pre-SRS. Pre-SRS had lower median planning target volume margin (0 mm vs 2 mm) and peripheral dose (14.5 Gy vs 18 Gy), but similar gross tumor volume (8.3 mL vs 9.2 mL, P = .85). The median imaging follow-up period was 24.6 months for alive patients. Multivariable analyses revealed no difference between groups for overall survival (P = .1), local recurrence (P = .24), and distant brain recurrence (P = .75). Post-SRS was associated with significantly higher rates of leptomeningeal disease (2 years: 16.6% vs 3.2%, P = .010) and symptomatic radiation necrosis (2 years: 16.4% vs 4.9%, P = .010).nnnCONCLUSIONnPre-SRS and Post-SRS for resected BM provide similarly favorable rates of local recurrence, distant brain recurrence, and overall survival, but with significantly lower rates of symptomatic radiation necrosis and leptomeningeal disease in the Pre-SRS cohort. A prospective clinical trial comparing these treatment approaches is warranted.nnnABBREVIATIONSnBM, brain metastasesCI, confidence intervalCTV, clinical target volumeDBR, distant brain recurrenceGTV, gross tumor volumeLC, local controlLMD, leptomeningeal diseaseLR, local recurrenceMVA, multivariable analysisOS, overall survivalPost-SRS, postoperative stereotactic radiosurgeryPre-SRS, preoperative stereotactic radiosurgeryPTV, planning target volumeRN, radiation necrosisSRN, symptomatic radiation necrosisSRS, stereotactic radiosurgeryWBRT, whole-brain radiation therapy.

Novel risk stratification score for predicting early distant brain failure and salvage whole-brain radiotherapy after stereotactic radiosurgery for brain metastases.

The purpose of this study was to evaluate predictors of early distant brain failure (DBF) and salvage whole‐brain radiotherapy (WBRT) after treatment with stereotactic radiosurgery (SRS) for brain metastases and create a clinically relevant risk score to stratify patients’ risk for these events.

Comparing pre-operative stereotactic radiosurgery (SRS) to post-operative whole brain radiation therapy (WBRT) for resectable brain metastases: a multi-institutional analysis

Pre-operative stereotactic radiosurgery (pre-SRS) has been shown as a viable treatment option for resectable brain metastases (BM). The aim of this study is to compare oncologic outcomes and toxicities for pre-SRS and post-operative WBRT (post-WBRT) for resectable BM. We reviewed records of consecutive patients who underwent resection of BM and either pre-SRS or post-WBRT between 2005 and 2013 at two institutions. Overall survival (OS) was calculated using the Kaplan–Meier method. Cumulative incidence was used for intracranial outcomes. Multivariate analysis (MVA) was performed using the Cox and Fine and Gray models, respectively. Overall, 102 patients underwent surgical resection of BM; 66 patients with 71 lesions received pre-SRS while 36 patients with 42 cavities received post-WBRT. Baseline characteristics were similar except for the pre-SRS cohort having more single lesions (65.2% vs. 38.9%, pu2009=u20090.001) and smaller median lesion volume (8.3xa0cc vs. 15.3xa0cc, pu2009=u20090.006). 1-year OS was similar between cohorts (58% vs. 56%, respectively) (pu2009=u20090.43). Intracranial outcomes were also similar (2-year outcomes, pre-SRS vs. post-WBRT): local recurrence: 24.5% vs. 25% (pu2009=u20090.81), distant brain failure (DBF): 53.2% vs. 45% (pu2009=u20090.66), and leptomeningeal disease (LMD) recurrence: 3.5% vs. 9.0% (pu2009=u20090.66). On MVA, radiation cohort was not independently associated with OS or any intracranial outcome. Crude rates of symptomatic radiation necrosis were 5.6 and 0%, respectively. OS and intracranial outcomes were similar for patients treated with pre-SRS or post-WBRT for resected BM. Pre-SRS is a viable alternative to post-WBRT for resected BM. Further confirmatory studies with neuro-cognitive outcomes comparing these two treatment paradigms are needed.

Single-Fraction Stereotactic Radiosurgery (SRS) Alone Versus Surgical Resection and SRS for Large Brain Metastases: A Multi-institutional Analysis

PURPOSEnStereotactic radiosurgery (SRS) dose is limited by brain metastasis (BM) size. The study goal was to retrospectively determine whether there is a benefit for intracranial outcomes and overall survival (OS) for gross total resection with single-fraction SRS versus SRS alone for patients with large BMs.nnnMETHODS AND MATERIALSnA large BM was defined as ≥4xa0cm3 (2xa0cm in diameter) prior to the study. We reviewed the records of consecutive patients treated with single-fraction SRS alone or surgery with preoperative or postoperative SRS between 2005 and 2013 from 2 institutions.nnnRESULTSnOverall, 213 patients with 223 treated large BMs were included; 66 BMs (30%) were treated with SRS alone and 157 (70%) with surgery and SRS (63 preoperatively and 94 postoperatively). The groups (SRS vs surgery and SRS) were well balanced except regarding lesion volume (median, 5.9xa0cm3 vs 9.6xa0cm3; P<.001), median number of BMs (1.5 vs 1, P=.002), median SRS dose (18xa0Gy vs 15xa0Gy, P<.001), and prior whole-brain radiation therapy (33% vs 5%, P<.001). The local recurrence (LR) rate was significantly lower with surgery and SRS (1-year LR rate, 36.7% vs 20.5%; P=.007). There was no difference in radiation necrosis (RN) by resection status, but there was a significantly increased RN rate with postoperative SRS versus with preoperative SRS and with SRS alone (1-year RN rate, 22.6% vs 5% and 12.3%, respectively; P<.001). OS was significantly higher with surgery and SRS (2-year OS rate, 38.9% vs 19.8%; P=.01). Both multivariate adjusted analyses and propensity score-matched analyses demonstrated similar results.nnnCONCLUSIONSnIn this retrospective study, gross total resection with SRS was associated with significantly reduced LR compared with SRS alone for patients with large BMs. Postoperative SRS was associated with the highest rate of RN. Surgical resection with SRS may improve outcomes in patients with a limited number of large BMs compared with SRS alone. Further studies are warranted.

Stereotactic Body Radiotherapy for Early- stage Non-small- cell Lung Cancer in Patients 80 Years and Older: A Multi- center Analysis

BACKGROUNDnStereotactic body radiotherapy (SBRT) is the standard of care for medically inoperable early-stage non-small-cell lung cancer. Despite the limited number of octogenarians and nonagenarians on trials of SBRT, its use is increasingly being offered in these patients, given the aging cancer population, medical fragility, or patient preference. Our purpose was to investigate the efficacy, safety, and survival of patientsxa0≥ 80 years old treated with definitive lung SBRT.nnnMETHODSnPatients who underwent SBRT were reviewed from 2009 to 2015 at 4 academic centers. Patients diagnosed atxa0≥ 80 years old were included. Kaplan-Meier and multivariate logistic regression and Cox proportional hazard regression analyses were performed. Recursive partitioning analysis was done to determine a subgroup of patients most likely to benefit from therapy.nnnRESULTSnA total of 58 patients were included, with a median age of 84.9 years (range, 80.1-95.2 years), a median follow-up time of 19.9 months (range, 6.9-64.9 months), a median fraction size of 10.0 Gy (range, 7.0-20.0 Gy), and a median number of fractions of 5.0 (range, 3.0-8.0 fractions). On multivariate analysis, higher Karnofsky performance status (KPS) was associated with higher local recurrence-free survival (hazard ratio [HR], 0.92; Pxa0< .01), regional recurrence-free survival (HR, 0.94; Pxa0< .01), and overall survival (HR, 0.91; Pxa0< .01). On recursive partitioning analysis, patients with KPSxa0≥ 75 had improved 3-year cancer-specific and overall survival (99.4% and 91.9%, respectively) compared with patients with KPSxa0< 75 (47.8% and 23.6%, respectively; Pxa0< .01).nnnCONCLUSIONnDefinitive lung SBRT for early-stage non-small-cell lung cancer was efficacious and safe in patientsxa0≥ 80 years old. Patients with a KPS ofxa0≥ 75 derived the most benefit from therapy.

Outcomes and patterns of failure for grade 2 meningioma treated with reduced-margin intensity modulated radiation therapy.

PURPOSEnThe purpose of this study was to evaluate intracranial control and patterns of local recurrence (LR) for grade 2 meningiomas treated with intensity modulated radiation therapy (IMRT) with limited total margin expansions of ≤1 cm.nnnMETHODS AND MATERIALSnWe reviewed records of patients with a neuropathological diagnosis of grade 2 meningioma who underwent IMRT at our institution between 2002 and 2012. Actuarial rates were determined by the Kaplan-Meier method from the end of RT. LR was defined as in-field if ≥90% of the recurrence was within the prescription isodose, out-of-field (marginal) if ≥90% was outside of the prescription isodose, and both if neither criterion was met.nnnRESULTSnBetween 2002 and 2012, a total of 54 consecutive patients underwent IMRT for grade 2 meningioma. Eight of these patients had total initial margins >1 cm and were excluded, leaving 46 patients for analysis. The median imaging follow-up period was 26.2 months (range, 7-107 months). The median dose for fractionated IMRT was 59.4 Gy (range, 49.2-61.2 Gy). Median clinical target volume (CTV), planning target volume (PTV), and total margin expansion were 0.5 cm, 0.3 cm, and 0.8 cm, respectively. LR occurred in 8 patients (17%), with 2-year and 3-year actuarial local control (LC) of 92% and 74%, respectively. Six of 8 patients (85%) had a known pattern of failure. Five patients (83%) had in-field LR; no patients had marginal LR; and 1 patient (17%) had both.nnnCONCLUSIONSnThe use of IMRT to treat grade 2 meningiomas with total initial margins (CTV + PTV) ≤1 cm did not appear to compromise outcomes or increase marginal failures compared with other modern retrospective series. Of the 46 patients who had margins ≤1 cm, none experienced marginal failure only. These results demonstrate efficacy and low risk of marginal failure after IMRT treatment of grade 2 meningiomas with reduced margins, warranting study within a prospective clinical trial.

External Validity of a Risk Stratification Score Predicting Early Distant Brain Failure and Salvage Whole Brain Radiotherapy after Stereotactic Radiosurgery for Brain Metastases

BACKGROUNDnA scoring system using pretreatment factors was recently published forxa0predicting the risk of early (≤6xa0months) distant brain failure (DBF) and salvage whole brain radiation therapy (WBRT) after stereotactic radiosurgery (SRS) alone. Four risk factors were identified: (1) lack of prior WBRT; (2) melanoma or breast histologic features; (3) multiple brain metastases; and (4) total volume of brain metastases <1.3xa0cm3, with each factor assigned 1 point. The purpose of this study was to assess the validity of this scoring system and its appropriateness for clinical use in an independent external patient population.nnnMETHODSnWe reviewed the records of 247 patients with 388 brain metastases treated with SRS between 2010 at 2013 at Levine Cancer Institute. The Press (Emory) risk score was calculated and applied to the validation cohort population, and subsequent risk groups were analyzed using cumulative incidence.nnnRESULTSnThe low-risk (LR) group had a significantly lower risk of early DBF than did the high-risk (HR) group (22.6% vs 44%, P=.004), but there was no difference between the HR and intermediate-risk (IR) groups (41.2% vs 44%, P=.79). Total lesion volume <1.3xa0cm3xa0(P=.004), malignant melanoma (P=.007), and multiple metastases (P<.001) were validated as predictors for early DBF. Prior WBRT and breast cancer histologic features did not retain prognostic significance. Risk stratification for risk of early salvage WBRT were similar, with a trend toward an increased risk for HR compared with LR (P=.09) but no difference between IR and HR (P=.53).nnnCONCLUSIONnThe 3-level Emory risk score was shown to not be externally valid, but the model was able to stratify between 2 levels (LR and not-LR [combined IR and HR]) for early (≤6xa0months) DBF. These results reinforce the importance of validating predictive models in independent cohorts. Further refinement of this scoring system with molecular information and in additional contemporary patient populations is warranted.

The use of Hypofractionated Radiosurgery for the Treatment of Intracranial Lesions Unsuitable for Single-Fraction Radiosurgery

Stereotactic radiosurgery (SRS) is commonly used in the treatment of brain metastases, benign tumors, and arteriovenous malformations (AVM). Single-fraction radiosurgery, though ubiquitous, is limited by lesion size and location. In these cases, hypofractionated radiosurgery (hfSRS) offers comparable efficacy and toxicity. We review the recent literature concerning hfSRS in the treatment of brain metastases, benign tumors, and AVMs that are poorly suited for single-fraction SRS. Published retrospective analyses suggest that local control rates for brain metastases and benign tumors, as well as the rates of AVM obliteration, following hfSRS treatment are comparable to those reported for single-fraction SRS. Additionally, the toxicities from hypofractionated treatment appear comparable to those seen with single-fractioned SRS to small lesions.

Preoperative Vs Postoperative Radiosurgery For Resected Brain Metastases: A Review

Patients who undergo surgical resection of brain metastases are at significant risk of cavity local recurrence without additional radiation therapy. Postoperative stereotactic radiosurgery (SRS) is a method of focal treatment to the cavity to maximize local control while minimizing the risk of neurocognitive detriment associated with whole brain radiation therapy. Recently published randomized trials have demonstrated the benefit of postoperative SRS in terms of cavity tumor control and preserving neurocognition. However, there are several potential drawbacks with postoperative SRS including a possible increase in symptomatic radiation necrosis because of the need for cavity margin expansion due to target delineation uncertainty, the variable postoperative clinical course and potential delay in administering postoperative SRS, and the theoretical risk of tumor spillage into cerebrospinal fluid at the time of surgery. Preoperative SRS is an alternative paradigm wherein SRS is delivered prior to surgical resection, which may effectively address some of these potential drawbacks. The goal of this review is to examine the rationale, technique, outcomes, evidence, and future directions for the use of SRS as an adjunct to surgical resection. This can be delivered as either preoperative or postoperative SRS with potential advantages and disadvantages to both approaches that will be discussed.

Hemorrhagic and Cystic Brain Metastases Are Associated With an Increased Risk of Leptomeningeal Dissemination After Surgical Resection and Adjuvant Stereotactic Radiosurgery

BACKGROUNDnBrain metastases (BM) treated with surgical resection and focal postoperative radiotherapy have been associated with an increased risk of subsequent leptomeningeal dissemination (LMD). BMs with hemorrhagic and/or cystic features contain less solid components and may therefore be at higher risk for tumor spillage during resection.nnnOBJECTIVEnTo investigate the association between hemorrhagic and cystic BMs treated with surgical resection and stereotactic radiosurgery and the risk of LMD.nnnMETHODSnOne hundred thirty-four consecutive patients with a single resected BM treated with adjuvant stereotactic radiosurgery from 2008 to 2016 were identified. Intracranial outcomes including LMD were calculated using the cumulative incidence model with death as a competing risk. Univariable analysis and multivariable analysis were assessed using the Fine & Gray model. Overall survival was analyzed using the Kaplan-Meier method.nnnRESULTSnMedian imaging follow-up was 14.2 mo (range 2.5-132 mo). Hemorrhagic and cystic features were present in 46 (34%) and 32 (24%) patients, respectively. The overall 12- and 24-mo cumulative incidence of LMD with death as a competing risk was 11.0 and 22.4%, respectively. On multivariable analysis, hemorrhagic features (hazard ratio [HR] 2.34, Pxa0=xa0.015), cystic features (HR 2.34, Pxa0=xa0.013), breast histology (HR 3.23, Pxa0=xa0.016), and number of brain metastases >1 (HR 2.09, Pxa0=xa0.032) were independently associated with increased risk of LMD.nnnCONCLUSIONnHemorrhagic and cystic features were independently associated with increased risk for postoperative LMD. Patients with BMs containing these intralesion features may benefit from alternative treatment strategies to mitigate this risk.