5-year outcomes after stereotactic ablative body radiotherapy for primary renal cell carcinoma: an individual patient data meta-analysis from IROCK (the International Radiosurgery Consortium of the Kidney).

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is a non-invasive treatment option for primary renal cell carcinoma, for which long-term data are awaited. The primary aim of this study was to report on long-term efficacy and safety of SABR for localised renal cell carcinoma. METHODS: This study was an individual patient data meta-analysis, for which patients undergoing SABR for primary renal cell carcinoma across 12 institutions in five countries (Australia, Canada, Germany, Japan, and the USA) were eligible. Eligible patients had at least 2 years of follow-up, were aged 18 years or older, had any performance status, and had no previous local therapy. Patients with metastatic renal cell carcinoma or upper-tract urothelial carcinoma were excluded. SABR was delivered as a single or multiple fractions of greater than 5 Gy. The primary endpoint was investigator-assessed local failure per the Response Evaluation Criteria in Solid Tumours version 1.1, and was evaluated using cumulative incidence functions. FINDINGS: 190 patients received SABR between March 23, 2007, and Sept 20, 2018. Single-fraction SABR was delivered in 81 (43%) patients and multifraction SABR was delivered in 109 (57%) patients. Median follow-up was 5·0 years (IQR 3·4-6·8). 139 (73%) patients were men, and 51 (27%) were women. Median age was 73·6 years (IQR 66·2-82·0). Median tumour diameter was 4·0 cm (IQR 2·8-4·9). 96 (75%) of 128 patients with available operability details were deemed inoperable by the referring urologist. 56 (29%) of 190 patients had a solitary kidney. Median baseline estimated glomerular filtration rate (eGFR) was 60·0 mL/min per 1·73 m2 (IQR 42·0-76·0) and decreased by 14·2 mL/min per 1·73 m2 (IQR 5·4-22·5) by 5 years post-SABR. Seven (4%) patients required dialysis post-SABR. The cumulative incidence of local failure at 5 years was 5·5% (95% CI 2·8-9·5) overall, with single-fraction SABR yielding fewer local failures than multifraction (Gray's p=0·020). There were no grade 3 toxic effects or treatment-related deaths. One (1%) patient developed an acute grade 4 duodenal ulcer and late grade 4 gastritis. INTERPRETATION: SABR is effective and safe in the long term for patients with primary renal cell carcinoma. Single-fraction SABR might yield less local failure than multifraction, but further evidence from randomised trials is needed to elucidate optimal treatment schedules. These mature data lend further support for renal SABR as a treatment option for patients unwilling or unfit to undergo surgery. FUNDING: None.

PA- and NP-led Ommaya clinics to manage leptomeningeal carcinomatosis.

OBJECTIVES: Physician assistants (PAs) and NPs are essential to quality care delivery. The need to demonstrate value and optimize PA and NP roles in neurology subspecialty clinics is unmet. We outline the development of a PA- and NP-led neuro-oncology procedural clinic and provide metrics to support the institutional and clinician value added. METHODS: We designed a PA- and NP-led Geisinger Ommaya Clinic (GOC) to manage leptomeningeal carcinomatosis (LMC) with defined clinician roles and the GOC treatment protocol. A retrospective review of 135 patients (2012-2019) compared survival outcomes for patients treated on the protocol compared with those treated off the protocol. RESULTS: Centralized care in the GOCs minimized shared physician encounters and improved PA and NP autonomy and utility. LMC therapy as part of the GOC protocol improved care continuity and survival outcomes. CONCLUSIONS: PA- and NP-led procedural clinics optimize use of these clinicians and open physician availability for nonprocedural duties. This research highlights the institutional patient and financial benefit while demonstrating the operational and leadership growth potential for PAs and NPs.

Early imaging marker of progressing glioblastoma: a window of opportunity.

PURPOSE: Therapeutic intervention at glioblastoma (GBM) progression, as defined by current assessment criteria, is arguably too late as second-line therapies fail to extend survival. Still, most GBM trials target recurrent disease. We propose integration of a novel imaging biomarker to more confidently and promptly define progression and propose a critical timepoint for earlier intervention to extend therapeutic exposure. METHODS: A retrospective review of 609 GBM patients between 2006 and 2019 yielded 135 meeting resection, clinical, and imaging inclusion criteria. We qualitatively and quantitatively analyzed 2000+ sequential brain MRIs (initial diagnosis to first progression) for development of T2 FLAIR signal intensity (SI) within the resection cavity (RC) compared to the ventricles (V) for quantitative inter-image normalization. PFS and OS were evaluated using Kaplan-Meier curves stratified by SI. Specificity and sensitivity were determined using a 2 × 2 table and pathology confirmation at progression. Multivariate analysis evaluated SI effect on the hazard rate for death after adjusting for established prognostic covariates. Recursive partitioning determined successive quantifiers and cutoffs associated with outcomes. Neurological deficits correlated with SI. RESULTS: Seventy-five percent of patients developed SI on average 3.4 months before RANO-assessed progression with 84% sensitivity. SI-positivity portended neurological decline and significantly poorer outcomes for PFS (median, 10 vs. 15 months) and OS (median, 20 vs. 29 months) compared to SI-negative. RC/V ratio ≥ 4 was the most significant prognostic indicator of death. CONCLUSION: Implications of these data are far-reaching, potentially shifting paradigms for glioma treatment response assessment, altering timepoints for salvage therapeutic intervention, and reshaping glioma clinical trial design.

Feasibility, safety, and utility of brain MRI for patients with non-MRI-conditioned CIED.

Feasibility, safety, and utility of brain MRI for patients with non-MRI-conditioned cardiac implantable electrical devices (CIEDs) remains controversial. While a growing number of studies have shown safe employment in select patients under strict protocols, there is an increasing clinical need for further off-label investigations. To assess the feasibility and utility of brain MRI in neurological and neurosurgical patients with non-MRI-conditioned CIEDs using off-label protocol. We retrospectively evaluated 126 patients with non-MRI-conditioned CIEDs referred to our hospital between 2014 to 2018 for MRI under an IRB-approved protocol. A total of 126 off-label brain MRI scans were performed. The mean age was 67.5 ± 13.0. Seventy percent of scans were performed on female patients. Indications for MRI are neurosurgical (45.2%), neurological (51.6%), and others (3.2%). MRI utilization for tumor cases was highest for tumor cases (68.3%), but employment was valuable for vascular (12.7%), deep brain stimulators (3.2%), and other cases (15.9%). In the tumor category, (37.2%) of the scans were performed for initial diagnosis and pre-surgical planning, (47.7%) for post-intervention evaluation/surveillance, (15.1%) for stereotactic radiosurgery treatment (CyberKnife). No clinical complications were encountered. No functional device complications of the CIED were identified during and after the MRI in 96.9% of the studies. A 49.6% of the off-label brain MRI scans performed led to a clinically significant decision and/or intervention for the patients. A 42.9% of obtained MRI studies did not change the plan of care. A 7.9% of post-scan decision-making data was not available. We demonstrate that off-label brain MRI scans performed on select patients under a strict protocol is feasible, safe, and relevant. Almost 50% of scans provided critical information resulting in clinical intervention of the patients.

Stereotactic Radiotherapy as a Treatment Option for Renal Tumors in the Solitary Kidney: A Multicenter Analysis from the IROCK.

PURPOSE: Stereotactic ablative radiotherapy is an emerging treatment for renal cell carcinoma. Our study objective was to evaluate this therapy in patients with a solitary kidney, focusing on oncologic and renal function outcomes. MATERIALS AND METHODS: We pooled individual patient data from 9 IROCK (International Radiosurgery Oncology Consortium for Kidney) institutions in Germany, Australia, the United States of America, Canada and Japan. Median followup was 2.6 years. Baseline characteristics and outcomes were compared between the solitary and bilateral kidney cohorts. Predictors of renal function after stereotactic ablative radiotherapy were assessed by logistic regression modeling. RESULTS: A total of 81 patients with a solitary kidney underwent stereotactic ablative radiotherapy. Mean age was 67.3 years and 97.5% of patients had good performance status, including ECOG (Eastern Cooperative Oncology Group) 0-1 or KPS (Karnofsky Performance Status) 70% or greater. Median tumor diameter was 3.7 cm (IQR 2.5-4.3) and 37% of tumors were 4 cm or greater. The 138 patients in the bilateral cohort harbored larger tumors and were older (p <0.001) with a lower baseline estimated glomerular filtration rate (p = 0.024). After stereotactic ablative radiotherapy in the solitary kidney cohort the mean ± SD estimated glomerular filtration rate decrease was -5.8 ± 10.8 ml per minute (-9%). No patient with a solitary kidney required dialysis. After stereotactic ablative radiotherapy a tumor size of 4 cm or greater was associated with an estimated glomerular filtration rate decrease of 15 ml per minute or greater (OR 4.2, p = 0.029). At 2 years the rates of local control, and progression-free, cancer specific and overall survival in the solitary cohort were 98.0%, 77.5%, 98.2% and 81.5%, respectively. There was no significant difference in renal function or oncologic outcomes between the cohorts (p >0.05). CONCLUSIONS: In this analysis of the IROCK database stereotactic ablative radiotherapy in patients with a solitary kidney had an acceptable impact on renal function and achieved excellent oncologic outcomes, similar to those in patients with bilateral kidneys. Thus, stereotactic ablative radiotherapy represents a viable treatment option in patients with renal cell carcinoma in a solitary kidney.

Pooled analysis of stereotactic ablative radiotherapy for primary renal cell carcinoma: A report from the International Radiosurgery Oncology Consortium for Kidney (IROCK).

BACKGROUND: Stereotactic ablative radiotherapy (SABR) is an emerging therapy for primary renal cell carcinoma. The authors assessed safety, efficacy, and survival in a multi-institutional setting. Outcomes between single-fraction and multifraction SABR were compared. METHODS: Individual patient data sets from 9 International Radiosurgery Oncology Consortium for Kidney institutions across Germany, Australia, the United States, Canada, and Japan were pooled. Toxicities were recorded using Common Terminology Criteria for Adverse Events, version 4.0. Patient, tumor, and treatment characteristics were stratified according to the number of radiotherapy fractions (single vs multiple). Survival outcomes were examined using Kaplan-Meier estimates and Cox proportional-hazards regression. RESULTS: Of 223 patients, 118 received single-fraction SABR, and 105 received multifraction SABR. The mean patient age was 72 years, and 69.5% of patients were men. There were 83 patients with grade 1 and 2 toxicity (35.6%) and 3 with grade 3 and 4 toxicities (1.3%). The rates of local control, cancer-specific survival, and progression-free survival were 97.8%, 95.7%, and 77.4%, respectively, at 2 years; and they were 97.8%, 91.9%, and 65.4%, respectively, at 4 years. On multivariable analysis, tumors with a larger maximum dimension and the receipt of multifraction SABR were associated with poorer progression-free survival (hazard ratio, 1.16 [P < .01] and 1.13 [P = .02], respectively) and poorer cancer-specific survival (hazard ratio, 1.28 [P < .01] and 1.33 [P = .01], respectively). There were no differences in local failure between the single-fraction cohort (n = 1) and the multifraction cohort (n = 2; P = .60). The mean ( ± standard deviation) estimated glomerular filtration rate at baseline was 59.9 ± 21.9 mL per minute, and it decreased by 5.5 ± 13.3 mL per minute (P < .01). CONCLUSIONS: SABR is well tolerated and locally effective for treating patients who have primary renal cell carcinoma and has an acceptable impact on renal function. An interesting observation is that patients who receive single-fraction SABR appear to be less likely to progress distantly or to die of cancer. Cancer 2018;124:934-42. © 2017 American Cancer Society.

Schwannoma of the trochlear nerve-an illustrated case series and a systematic review of management.

Schwannomas of cranial nerves in the absence of systemic neurofibromatosis are relatively rare. Among these, schwannomas of the trochlear nerve are even less common. They can be found incidentally or when they cause diplopia or other significant neurological deficits. Treatment options include observation only, neuro-ophthalmological intervention, and/or neurosurgical management via resection or sterotactic radiosurgery (SRS). In recent years, the latter has become an attractive therapeutic tool for a number of benign skull base neoplasm including a small number of reports on its successful use for trochlear Schwannomas. However, no treatment algorithm for the management of these tumors has been proposed so far. The goal of this manuscript is to illustrate a case series of this rare entity and to suggest a rational treatment algorithm for trochlear schwannomas, based on our institutional experience of recent cases, and a pertinent review of the literature. Including our series of 5 cases, a total of 85 cases reporting on the management of trochlear schwannomas have been published. Of those reported, less than half (40 %) of patients underwent surgical resection, whereas the remainder were managed conservatively or with SRS. Seventy-six percent (65/85) of the entire cohort presented with diplopia, which was the solitary symptom in over half of the cases (n = 39). All patients who presented with symptoms other than diplopia or headaches as solitary symptoms underwent surgical resection. Patients in the non-surgical group were mostly male (M/F = 3.5:1), presented at an older age and had shorter mean diameter (4.6 vs. 30.4 mm, p < 0.0001) when compared to the surgical group. Twelve patients in the entire cohort were treated with SRS, none of whom had undergone surgical resection before or after radiation treatment. Trochlear schwannoma patients without systemic neurofibromatosis are rare and infrequently reported in the literature. Of those, patients harboring symptomatic trochlear Schwannomas do not form a single homogenous group, but fall into two rather distinct subgroups regarding demographics and clinical characteristics. Among those patients in need of intervention, open microsurgical resection as well as less invasive treatment options exist, which all aim at safe relief of symptoms and prevention of progression. Both open microsurgical removal as well as SRS can achieve good long-term local control. Consequently, a tailored multidisciplinary treatment algorithm, based on the individual presentation and tumor configuration, is proposed.

Meningiomas in pregnancy: timing of surgery and clinical outcomes as observed in 104 cases and establishment of a best management strategy.

BACKGROUND: There is a strong correlation between the level of circulating female sex hormones and the parturient growth of meningiomas. As a result, rapid changes in meningioma size occur during pregnancy, putting both the mother and fetus at risk. Large, symptomatic meningiomas require surgical resection, regardless of the status of pregnancy. However, the preferred timing of such complex intervention is a matter of debate. The rarity of this clinical scenario and the absence of prospective trials make it difficult to reach evidence-based conclusions. The aim of this study was to create evidence-based management guidelines for timing of surgery for pregnancy-related intracranial meningiomas. METHOD: The English literature from 1990 to 2016 was systematically reviewed according to PRISMA guidelines for all surgical cases of pregnancy-related intracranial meningiomas. Cases were divided into two groups: patients who have had surgery during pregnancy and delivered thereafter (group A) and patients who delivered first (group B). Groups were compared for demographic, clinical and radiological features, as well as for neurosurgical, obstetrical and neonatological outcomes. Statistical analysis was performed to assess differences. RESULTS: A total of 104 surgical cases were identified and reviewed, of which 86 were suitable for comparison and statistical analysis. Thirty-five patients (40%) underwent craniotomy for resection during pregnancy or at delivery (group A) and 51 patients (60%) underwent surgery after delivery (group B). Groups showed no significant differences in characteristics such as age at diagnosis, number of gestations, presenting symptoms, tumor site and tumor size. Despite a comparable distribution over the gestational trimesters, group A had significantly more patients diagnosed prior to the 27th gestational week (46 vs 17.5%, p = 0.0075). Group A was also associated with a significantly higher rate of both emergent craniotomies (40 vs 19.6%, p = 0.0048) and emergent Caesarian deliveries (47 vs 17.8%, p = 0.00481). The time from diagnosis to surgery was significantly longer in group B (11 weeks vs 1 week in group A, p = 0.0013). The rate of premature delivery was high but similar in both groups (∼70%). Risks of maternal mortality or fetal mortality were associated with group A (odds ratio = 14.7), but did not reach statistical significance. CONCLUSIONS: While surgical resection of meningioma during pregnancy may be associated with increased maternal and fetal mortalities, the overall neurosurgical, obstetrical and neonatological outcomes, as well as many clinical characteristics, are similar to patients undergoing resection postpartum. We believe that fetal survival chances have a significant impact on decision-making, as patients diagnosed at a later stage in pregnancy (≥27th week of gestation) were more likely to undergo delivery first. This complicated clinical scenario requires the close cooperation of multiple disciplines. While the mother's health and well-being should always be paramount in guiding management, we hope that the overall good outcomes observed by this systematic review will encourage colleagues to aim for term pregnancies whenever possible in order to reduce prematurity-related problems.

Stereotactic body radiotherapy for unresected pancreatic cancer: A nationwide review.

BACKGROUND: The role of conventional radiotherapy in the management of pancreatic cancer has yet to be elucidated. Over the past decade, stereotactic body radiotherapy (SBRT) has emerged as a novel therapeutic option in pancreatic cancer care. This study evaluated the survival impact of SBRT on patients with unresected pancreatic cancer. METHODS: The National Cancer Data Base was queried for unresected patients who received chemotherapy for nonmetastatic pancreatic adenocarcinoma between 2004 and 2012. Four treatment groups were identified: chemotherapy alone, chemotherapy combined with external-beam radiotherapy (EBRT), chemotherapy combined with intensity-modulated radiotherapy (IMRT), and chemotherapy combined with SBRT. Propensity score models predicting the odds of receiving SBRT were created to control for potential selection bias, and patients were matched by propensity scores. The survival analysis was performed with the Kaplan-Meier method. RESULTS: A total of 14,331 patients met the inclusion criteria. Chemotherapy alone was delivered to 5464 patients (38.1%); 6418 (44.8%), 322 (2.3%), and 2127 (14.8%) received chemotherapy along with EBRT, IMRT, and SBRT, respectively. The unadjusted median survival before matching was 9.9, 10.9, 12.0, and 13.9 months for patients treated with chemotherapy, EBRT, IMRT, and SBRT, respectively. In separate matched analyses, SBRT remained superior to chemotherapy alone (log-rank P < .0001) and EBRT (log-rank P = .0180). After matching, survival did not differ between patients receiving IMRT and patients receiving SBRT (log-rank P = .0492). CONCLUSIONS: SBRT is associated with a significantly better outcome than chemotherapy alone or in conjunction with traditional EBRT. These results support the idea that SBRT is a promising treatment approach for patients with unresected pancreatic cancer. Cancer 2017;123:4158-4167. © 2017 American Cancer Society.

Consensus statement from the International Radiosurgery Oncology Consortium for Kidney for primary renal cell carcinoma.

AIM: To provide a multi-institutional consensus document for stereotactic body radiotherapy of primary renal cell carcinoma. MATERIALS & METHODS: Eight international institutions completed a 65-item survey covering patient selection, planning/treatment aspects and response evaluation. RESULTS: All centers treat patients with pre-existing hypertension and solitary kidneys. Five institutions apply size constraints of 5-8 cm. The total planning target volume expansion is 3-10 mm. All institutions perform pretreatment imaging verification, while seven institutions perform some form of intrafractional monitoring. Number of fractions used are 1-12 to a total dose of 25 Gy-80 GyE. Imaging follow-up for local tumor response includes computed tomography (n = 8), PET-computed tomography (n = 1) and MRI (n = 5). Follow-up frequency is 3-6 months for the first 2 years and 3-12 months for subsequent 3 years. CONCLUSION: Key methods for safe implementation and practice for stereotactic body radiotherapy kidney have been identified and may aid standardization of treatment delivery.

Stereotactic body radiotherapy (SBRT) reirradiation for pelvic recurrence from colorectal cancer.

BACKGROUND AND OBJECTIVES: When surgery is not adequate or feasible, stereotactic body radiotherapy (SBRT) reirradiation has been used for recurrent cancers. We report the outcomes of a series of patients with pelvic recurrences from colorectal cancer reirradiated with SBRT. METHODS: The Cyberknife(TM) Robotic Stereotactic Radiosurgery system with fiducial based real time tracking was used. Patients were followed with imaging of the pelvis. RESULTS: Four women and 14 men with 22 lesions were included. The mean dose was 25 Gy in median of five fractions. The mean prescription isodose was 77%, with a median maximum dose of 32.87 Gy. There were two local failures, with a crude local control rate of 89%. The median overall survival was 43 months. One patient had small bowel perforation and required surgery (Grade IV), two patients had symptomatic neuropathy (1 Grade III) and one patient developed hydronephrosis from ureteric fibrosis requiring a stent (Grade III). CONCLUSIONS: Local recurrence in the pelvis after modern combined modality treatment for colorectal cancer is rare. However it presents a therapeutic dilemma when it occurs; often symptomatic and eventually life threatening. SBRT can be a useful non-surgical modality to control pelvic recurrences after prior radiation for colorectal cancer.

Radiation Therapy in the Management of Malignant Melanoma.

The initial treatment for primary and locoregional melanoma is surgery. Systemic therapy, and more recently immune therapy, has been the mainstay in the adjuvant and particularly the metastatic setting. Aside from palliation, there is a limited role for definitive radiation therapy for melanoma. However, in the adjuvant setting, postoperative radiation can improve locoregional disease control, albeit with potential toxicity and limited survival benefit. Stereotactic radiosurgery plays a vital role in the treatment of limited brain and extracranial metastasis.

Best of the Radiosurgery Society® Scientific Meeting 2014: stereotactic radiosurgery/stereotactic body radiotherapy treatment of extracranial and intracranial lesions.

The SRS/SBRT Scientific Meeting 2014, Minneapolis, MN, USA, 7-10 May 2014. The Radiosurgery Society(®), a professional medical society dedicated to advancing the field of stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT), held the international Radiosurgery Society Scientific Meeting, from 7-10 May 2014 in Minneapolis (MN, USA). This year's conference attracted over 400 attendants from around the world and featured over 100 presentations (46 oral) describing the role of SRS/SBRT for the treatment of intracranial and extracranial malignant and nonmalignant lesions. This article summarizes the meeting highlights for SRS/SBRT treatments, both intracranial and extracranial, in a concise review.

Hypofractionated Stereotactic Radiation Therapy Dosimetric Tolerances for the Inferior Aspect of the Brachial Plexus: A Systematic Review.

We sought to systematically review and summarize dosimetric factors associated with radiation-induced brachial plexopathy (RIBP) after stereotactic body radiation therapy (SBRT) or hypofractionated image guided radiation therapy (HIGRT). From published studies identified from searches of PubMed and Embase databases, data quantifying risks of RIBP after 1- to 10-fraction SBRT/HIGRT were extracted and summarized. Published studies have reported <10% risks of RIBP with maximum doses (Dmax) to the inferior aspect of the brachial plexus of 32 Gy in 5 fractions and 25 Gy in 3 fractions. For 10-fraction HIGRT, risks of RIBP appear to be low with Dmax < 40 to 50 Gy. For a given dose value, greater risks are anticipated with point volume-based metrics (ie, D0.03-0.035cc: minimum dose to hottest 0.03-0.035 cc) versus Dmax. With SBRT/HIGRT, there were insufficient published data to predict risks of RIBP relative to brachial plexus dose-volume exposure. Minimizing maximum doses and possibly volume exposure of the brachial plexus can reduce risks of RIBP after SBRT/HIGRT. Further study is needed to better understand the effect of volume exposure on the brachial plexus and whether there are location-specific susceptibilities along or within the brachial plexus structure.

High-volume prostate biopsy core involvement is not associated with an increased risk of cancer recurrence following 5-fraction stereotactic body radiation therapy monotherapy.

PURPOSE: Percentage of positive cores involved on a systemic prostate biopsy has been established as a risk factor for adverse oncologic outcomes and is a National Comprehensive Cancer Network (NCCN) independent parameter for unfavorable intermediate-risk disease. Most data from a radiation standpoint was published in an era of conventional fractionation. We explore whether the higher biological dose delivered with SBRT can mitigate this risk factor. METHODS: A large single institutional database was interrogated to identify all patients diagnosed with localized prostate cancer (PCa) treated with 5-fraction SBRT without ADT. Pathology results were reviewed to determine detailed core involvement as well as Gleason score (GS). High-volume biopsy core involvement was defined as ≥ 50%. Weighted Gleason core involvement was reviewed, giving higher weight to higher-grade cancer. The PSA kinetics and oncologic outcomes were analyzed for association with core involvement. RESULTS: From 2009 to 2018, 1590 patients were identified who underwent SBRT for localized PCa. High-volume core involvement was a relatively rare event observed in 19% of our cohort, which was observed more in patients with small prostates (p < 0.0001) and/or intermediate-risk disease (p = 0.005). Higher PSA nadir was observed in those patients with low-volume core involvement within the intermediate-risk cohort (p = 0.004), which was confirmed when core involvement was analyzed as a continuous variable weighted by Gleason score (p = 0.049). High-volume core involvement was not associated with biochemical progression (p = 0.234). CONCLUSIONS: With a median follow-up of over 4 years, biochemical progression was not associated with pretreatment high-volume core involvement for patients treated with 5-fraction SBRT alone. In the era of prostate SBRT and MRI-directed prostate biopsies, the use of high-volume core involvement as an independent predictor of unfavorable intermediate risk disease should be revisited.

A phase I study of lapatinib with whole brain radiotherapy in patients with Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer brain metastases.

Brain metastases are common in patients with advanced, Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer. We evaluated the maximum tolerated dose (MTD) and feasibility of lapatinib given concurrently with whole brain radiotherapy (WBRT). Eligible patients had (HER2)-positive breast cancer and ≥1 brain metastasis. Patients received lapatinib 750 mg twice on day one followed by 1000, 1250, or 1500 mg once daily. WBRT (37.5 Gy, 15 fractions) began 1-8 days after starting lapatinib. Lapatinib was continued through WBRT. Following WBRT, patients received trastuzumab 2 mg/kg weekly and lapatinib 1000 mg once daily. The regimen would be considered feasible if <3/27 pts treated at the MTD experienced a dose-limiting toxicity (DLT). Thirty-five patients were enrolled; 17 % had central nervous disease (CNS) only. During dose escalation, no patients receiving 1,000 or 1,250 mg and two of five patients receiving 1,500 mg experienced DLTs (grade 3 mucositis and rash). Overall, 7/27 patients at 1,250 mg (MTD) had DLTs: grade 3 rash (n = 2), diarrhea (n = 2), hypoxia (n = 1), and grade 4 pulmonary embolus (n = 2). Among 28 evaluable patients, the CNS objective response rate (ORR) was 79 % [95% confidence interval (CI) 59-92 %] by pre-specified volumetric criteria; 46 % remained progression-free (CNS or non-CNS) at 6 months. The study did not meet the pre-defined criteria for feasibility because of toxicity, although the relationship between study treatment and some DLTs was uncertain. Given the high ORR, concurrent lapatinib-WBRT could still be considered for future study with careful safety monitoring.

Efficacy and Safety of Primary Stereotactic Radiosurgery in Patients With Intraventricular Meningiomas.

Purpose: Primary stereotactic radiosurgery for intraventricular meningiomas remains controversial owing to the potential for life-threatening peritumoral edema and lack of long-term follow-up data. We review the literature and present the largest series to assess efficacy and safety of primary stereotactic radiosurgery. Methods and Materials: A systematic review of the literature for primary stereotactic radiosurgery for intraventricular meningiomas was conducted. The retrospective series presented here comprised 33 patients who received primary stereotactic radiosurgery between 1999 and 2015 for a radiologically detected intraventricular meningioma. Demographic, diagnostic, and therapeutic data were extracted from medical records, imaging, and treatment-planning systems. Both standalone and pooled analysis were performed. Results: The mean patient age was 53 years, and 24 patients (73%) were female. The median Karnofsky performance status pretreatment was 80 (range, 60-100). The majority of lesions were located in the lateral ventricles (n = 32; 97%). The mean tumor volume was 8.7 cm3 (range, 0.6-44.55 cm3). The mean delivered dose was 1390.9 cGy. Complete imaging follow-up data were available for 21 patients (64%). Of those, 14 (67%) showed partial or marginal response, 7 (33%) had stable disease, and no patient progressed per Response Assessment in Neuro-Oncology criteria. On last follow-up, 32 patients (97%) had significant improvement in performance status and a decrease in pretreatment symptoms. No high-grade Common Terminology Criteria for Adverse Events (version 5.0) toxicity was observed with the dose range employed. Conclusions: Primary stereotactic radiosurgery for intraventricular meningiomas shows excellent treatment efficacy and low toxicity in patients with a long follow-up period. The best therapeutic algorithm remains to be established leveraging further clinical investigation.

Radiation-induced inferior brachial plexopathy after stereotactic body radiotherapy: Pooled analyses of risks.

INTRODUCTION: Radiation-induced brachial plexopathy (RIBP), resulting in symptomatic motor or sensory deficits of the upper extremity, is a risk after exposure of the brachial plexus to therapeutic doses of radiation. We sought to model dosimetric factors associated with risks of RIBP after stereotactic body radiotherapy (SBRT). METHODS: From a prior systematic review, 4 studies were identified that included individual patient data amenable to normal tissue complication probability (NTCP) modelling after SBRT for apical lung tumors. Two probit NTCP models were derived: one from 4 studies (including 221 patients with 229 targets and 18 events); and another from 3 studies (including 185 patients with 192 targets and 11 events) that similarly contoured the brachial plexus. RESULTS: NTCP models suggest ≈10% risks associated with brachial plexus maximum dose (Dmax) of ∼32-34 Gy in 3 fractions and ∼40-43 Gy in 5 fractions. RIBP risks increase with increasing brachial plexus Dmax. Compared to previously published data from conventionally-fractionated or moderately-hypofractionated radiotherapy for breast, lung and head and neck cancers (which tend to utilize radiation fields that circumferentially irradiate the brachial plexus), SBRT (characterized by steep dose gradients outside of the target volume) exhibits a much less steep dose-response with brachial plexus Dmax > 90-100 Gy in 2-Gy equivalents. CONCLUSIONS: A dose-response for risk of RIBP after SBRT is observed relative to brachial plexus Dmax. Comparisons to data from less conformal radiotherapy suggests potential dose-volume dependences of RIBP risks, though published data were not amenable to NTCP modelling of dose-volume measures associated with RIBP after SBRT.

Pre-operative stereotactic radiosurgery for cerebral metastatic disease: A retrospective dose-volume study.

BACKGROUND AND PURPOSE: Stereotactic radiosurgery (SRS) after maximal safe resection is an accepted treatment strategy for patients with cerebral metastatic disease. Despite its high conformality profile, the incidence of radionecrosis (RN) remains high. SRS delivered pre-operatively could be associated with a reduced incidence of RN. We sought to evaluate whether neoadjuvant SRS could reduce radiotherapy doses in a cohort of patients treated with post-operative SRS. METHODS: A cohort of 47 brain metastases (BM) treated at 2 academic institutions was retrospectively analyzed. Subjects underwent surgical extirpation of BMs and subsequent SRS to surgical bed. Post-operative volumetric and dosimetric data was collected from records or recreations of delivered plans; pre-operative data were derived from hypothetical radiotherapy courses and compared using Wilcoxon signed-rank tests. RESULTS: Higher planned tumor volume post-operatively (median[IQR] 12.28 [6.54, 18.69]cc vs 10.20 [4.53, 21.70]cc respectively, p = 0.4150) was observed. The median prescribed radiotherapy dose (DRx) was 16 Gy pre-operatively and 24 Gy post-operatively (p < 0.0001). Further investigations revealed improved pre-operative conformity index (1.23[1.20, 1.29] vs 1.29[1.23, 1.39], p = 0.0098) and gradient index (2.72[2.59, 2.98] vs 2.94[2.69, 3.47], p = 0.0004). A significant difference was found in normal brain tissue exposed to 10 Gy (12.97[6.78, 25.54]cc vs 32.13[19.42, 48.40]cc, p < 0.0001), 12 Gy (9.31[4.56, 17.43]cc vs 23.80[14.74, 36.56]cc, p < 0.0001), and 14 Gy (5.62[3.23, 11.61]cc vs 17.47[9.00, 28.31]cc, p < 0.0001), favoring pre-operative SRS. CONCLUSIONS: Neoadjuvant SRS is associated reduced DRx, better conformality profile and decreased radiation to normal tissue. These findings could support the use of neoadjuvant SRS for the treatment of BMs.

Stereotactic Body Radiation Therapy for the Curative Treatment of Prostate Cancer in Ultralarge (≥100 cc) Glands.

PURPOSE: Historically, toxicity concerns have existed in patients with large prostate glands treated with radiation therapy, particularly brachytherapy. There are questions whether this risk extends to stereotactic body radiation therapy (SBRT). In this retrospective review, we examine clinical outcomes of patients with prostate glands ≥100 cc treated curatively with SBRT. METHODS AND MATERIALS: We retrospectively analyzed a large institutional database to identify patients with histologically confirmed localized prostate cancer in glands ≥100 cc, who were treated with definitive-robotic SBRT. Prostate volume (PV) was determined by treatment planning magnetic resonance imaging. Toxicity was measured using Common Terminology Criteria for Adverse Events, version 5.0. Many patients received the Expanded Prostate Cancer Index Composite Quality of Life questionnaires. Minimum follow-up (FU) was 2 years. RESULTS: Seventy-one patients were identified with PV ≥100 cc. Most had grade group (GG) 1 or 2 (41% and 37%, respectively) disease. All patients received a total dose of 3500 to 3625 cGy in 5 fractions. A minority (27%) received androgen deprivation therapy (ADT), which was used for gland size downsizing in only 10% of cases. Nearly half (45%) were taking GU medications for urinary dysfunction before RT. Median toxicity FU was 4.0 years. Two-year rates of grade 1+ genitourinary (GU), grade 1+ gastrointestinal (GI), and grade 2+ GU toxicity were 43.5%, 15.9%, and 30.4%, respectively. Total grade 3 GU toxicities were very limited (2.8%). There were no grade 3 GI toxicities. On logistic regression analysis, pretreatment use of GU medications was significantly associated with increased rate of grade 2+ GU toxicity (odds ratio, 3.19; P = .024). Furthermore, PV (analyzed as a continuous variable) did not have an effect on toxicity, quality of life, or oncologic outcomes. CONCLUSIONS: With early FU, ultra large prostate glands do not portend increased risk of high-grade toxicity after SBRT but likely carry an elevated risk of low-grade GU toxicity.