Impact of Cochlear Dose on Hearing Preservation Following Stereotactic Radiosurgery in Treatment of Vestibular Schwannomas: A Multi-Center Study.

OBJECTIVE: Stereotactic radiosurgery (SRS) is a well-established treatment for vestibular schwannomas (VS). Hearing loss remains a main morbidity of VS and its treatments, including SRS. The effects of radiation parameters of SRS on hearing remain unknown. The goal of this study is to determine the effect of tumor volume, patient demographics, pretreatment hearing status, cochlear radiation dose, total tumor radiation dose, fractionation, and other radiotherapy parameters on hearing deterioration. METHODS: Multicenter retrospective analysis of 611 patients who underwent SRS for VS from 1990-2020 and had pre- and post-treatment audiograms. RESULTS: Pure tone averages (PTAs) increased and word recognition scores (WRSs) decreased in treated ears at 12-60 months while remaining stable in untreated ears. Higher baseline PTA, higher tumor radiation dose, higher maximum cochlear dose, and usage of single fraction resulted in higher post radiation PTA; WRS was only predicted by baseline WRS and age. Higher baseline PTA, single fraction treatment, higher tumor radiation dose, and higher maximum cochlear dose resulted in a faster deterioration in PTA. Below a maximum cochlear dose of 3 Gy, there were no statistically significant changes in PTA or WRS. CONCLUSIONS: Decline of hearing at one year in VS patients after SRS is directly related to maximum cochlear dose, single versus 3-fraction treatment, total tumor radiation dose, and baseline hearing level. The maximum safe cochlear dose for hearingtbrowd preservation at one year is 3 Gy, and the use of 3 fractions instead of one fraction was better at preserving hearing.

NCCN Guidelines® Insights: Central Nervous System Cancers, Version 2.2022.

The NCCN Guidelines for Central Nervous System (CNS) Cancers focus on management of the following adult CNS cancers: glioma (WHO grade 1, WHO grade 2-3 oligodendroglioma [1p19q codeleted, IDH-mutant], WHO grade 2-4 IDH-mutant astrocytoma, WHO grade 4 glioblastoma), intracranial and spinal ependymomas, medulloblastoma, limited and extensive brain metastases, leptomeningeal metastases, non-AIDS-related primary CNS lymphomas, metastatic spine tumors, meningiomas, and primary spinal cord tumors. The information contained in the algorithms and principles of management sections in the NCCN Guidelines for CNS Cancers are designed to help clinicians navigate through the complex management of patients with CNS tumors. Several important principles guide surgical management and treatment with radiotherapy and systemic therapy for adults with brain tumors. The NCCN CNS Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's most recent recommendations regarding molecular profiling of gliomas.

Long-Term Results of a Phase 1 Dose-Escalation Trial and Subsequent Institutional Experience of Single-Fraction Stereotactic Ablative Radiation Therapy for Liver Metastases.

PURPOSE: We report long-term outcomes from our phase 1 dose-escalation study to determine the maximum tolerated dose of single-fraction liver SABR pooled with our subsequent single institutional experience with patients treated postprotocol at the highest dose level (40 Gy) established from the phase 1 study. METHODS AND MATERIALS: Patients with liver metastases from solid tumors located outside of the central liver zone were treated with single-fraction SABR on a phase 1 dose escalation trial. At least 700 cc of normal liver had to receive <9.1 Gy. Seven patients with 10 liver metastases received the initial prescription dose of 35 Gy, and dose was then escalated to 40 Gy for 7 more patients with 7 liver metastases. An additional 19 postprotocol patients with 22 liver metastases were treated to 40 Gy in a single fraction. Patients were followed for toxicity and underwent serial imaging to assess local control. RESULTS: Median imaging follow-up for the combined cohort (n = 33, 39 lesions) was 25.9 months; 38.9 months for protocol patients and 20.2 months for postprotocol patients. Median lesion size was 2.0 cm (range, 0.5-5.0 cm). There were no dose-limiting toxicities observed for protocol patients, and only 3 grade 2 toxicities were observed in the entire cohort, with no grade ≥3 toxicities attributable to treatment. Four-year actuarial local control of irradiated lesions in the entire cohort was 96.6%, 100% in the protocol group and 92.9% in the subsequent patients. Two-year overall survival for all treated patients was 82.0%. CONCLUSIONS: For selected patients with liver metastases, single-fraction SABR at doses of 35 and 40 Gy was safe and well-tolerated, and shows excellent local control with long-term follow-up; results in subsequent patients treated with single-fraction SABR doses of 40 Gy confirmed our earlier results.

Phase II trial of hippocampal-sparing whole brain irradiation with simultaneous integrated boost for metastatic cancer.

BACKGROUND: Advanced radiotherapeutic treatment techniques limit the cognitive morbidity associated with whole-brain radiotherapy (WBRT) for brain metastasis through avoidance of hippocampal structures. However, achieving durable intracranial control remains challenging. METHODS: We conducted a single-institution single-arm phase II trial of hippocampal-sparing whole brain irradiation with simultaneous integrated boost (HSIB-WBRT) to metastatic deposits in adult patients with brain metastasis. Radiation therapy consisted of intensity-modulated radiation therapy delivering 20 Gy in 10 fractions over 2-2.5 weeks to the whole brain with a simultaneous integrated boost of 40 Gy in 10 fractions to metastatic lesions. Hippocampal regions were limited to 16 Gy. Cognitive performance and cancer outcomes were evaluated. RESULTS: A total of 50 patients, median age 60 years (interquartile range, 54-65), were enrolled. Median progression-free survival was 2.9 months (95% CI: 1.5-4.0) and overall survival was 9 months. As expected, poor survival and end-of-life considerations resulted in a high exclusion rate from cognitive testing. Nevertheless, mean decline in Hopkins Verbal Learning Test-Revised delayed recall (HVLT-R DR) at 3 months after HSIB-WBRT was only 10.6% (95% CI: -36.5‒15.3%). Cumulative incidence of local and intracranial failure with death as a competing risk was 8.8% (95% CI: 2.7‒19.6%) and 21.3% (95% CI: 10.7‒34.2%) at 1 year, respectively. Three grade 3 toxicities consisting of nausea, vomiting, and necrosis or headache were observed in 3 patients. Scores on the Multidimensional Fatigue Inventory 20 remained stable for evaluable patients at 3 months. CONCLUSIONS: HVLT-R DR after HSIB-WBRT was significantly improved compared with historical outcomes in patients treated with traditional WBRT, while achieving intracranial control similar to patients treated with WBRT plus stereotactic radiosurgery (SRS). This technique can be considered in select patients with multiple brain metastases who cannot otherwise receive SRS.

A web-based brain metastases segmentation and labeling platform for stereotactic radiosurgery.

PURPOSE: Stereotactic radiosurgery (SRS) has become a standard of care for patients' with brain metastases (BMs). However, the manual multiple BMs delineation can be time-consuming and could create an efficiency bottleneck in SRS workflow. There is a clinical need for automatic delineation and quantitative evaluation tools. In this study, building on our previous developed deep learning-based segmentation algorithms, we developed a web-based automated BMs segmentation and labeling platform to assist the SRS clinical workflow. METHOD: This platform was developed based on the Django framework, including a web client and a back-end server. The web client enables interactions as database access, data import, and image viewing. The server performs the segmentation and labeling tasks including: skull stripping; deep learning-based BMs segmentation; and affine registration-based BMs labeling. Additionally, the client can display BMs contours with corresponding atlas labels, and allows further postprocessing tasks including: (a) adjusting window levels; (b) displaying/hiding specific contours; (c) removing false-positive contours; (d) exporting contours as DICOM RTStruct files; etc. RESULTS: We evaluated this platform on 10 clinical cases with BMs number varied from 12-81 per case. The overall operation took about 4-5 min per patient. The segmentation accuracy was evaluated between the manual contour and automatic segmentation with several metrics. The averaged center of mass shift was 1.55 ± 0.36 mm, the Hausdorff distance was 2.98 ± 0.63 mm, the mean of surface-to-surface distance (SSD) was 1.06 ± 0.31 mm, and the standard deviation of SSD was 0.80 ± 0.16 mm. In addition, the initial averaged false-positive over union (FPoU) and false-negative rate (FNR) were 0.43 ± 0.19 and 0.15 ± 0.10 respectively. After case-specific postprocessing, the averaged FPoU and FNR were 0.19 ± 0.10 and 0.15 ± 0.10 respectively. CONCLUSION: The evaluated web-based BMs segmentation and labeling platform can substantially improve the clinical efficiency compared to manual contouring. This platform can be a useful tool for assisting SRS treatment planning and treatment follow-up.

Fundamentals of Radiation Oncology for Neurologic Imaging.

Although the physical and biologic principles of radiation therapy have remained relatively unchanged, a technologic renaissance has led to continuous and ever-changing growth in the field of radiation oncology. As a result, medical devices, techniques, and indications have changed considerably during the past 20-30 years. For example, advances in CT and MRI have revolutionized the treatment planning process for a variety of central nervous system diseases, including primary and metastatic tumors, vascular malformations, and inflammatory diseases. The resultant improved ability to delineate normal from abnormal tissue has enabled radiation oncologists to achieve more precise targeting and helped to mitigate treatment-related complications. Nevertheless, posttreatment complications still occur and can pose a diagnostic challenge for radiologists. These complications can be divided into acute, early-delayed, and late-delayed complications on the basis of the time that they manifest after radiation therapy and include leukoencephalopathy, vascular complications, and secondary neoplasms. The different irradiation technologies and applications of these technologies in the brain, current concepts used in treatment planning, and essential roles of the radiation oncologist in the setting of brain disease are reviewed. In addition, relevant imaging findings that can be used to delineate the extent of disease before treatment, and the expected posttreatment imaging changes are described. Common and uncommon complications related to radiation therapy and the associated imaging manifestations also are discussed. Familiarity with these entities may aid the radiologist in making the diagnosis and help guide appropriate management. ©RSNA, 2020.

Unique Patterns of Distant Metastases in HPV-Positive Head and Neck Cancer.

BACKGROUND: HPV-positive head and neck squamous cell carcinoma (HPV+ HNSCC) demonstrates favorable outcomes compared to HPV-negative SCC, but distant metastases (DM) still occur. The pattern of DM in HPV+ HNSCC is unclear. METHODS: 1,494 HNSCC patients were treated from 2006 to 2012. Recurrence time and metastatic sites in HPV+ HNSCC (Group 1) were compared to patients with HPV-negative/unknown cancers arising in the hypopharynx, larynx, or glottis (Group 2) as well as to patients with HPV-negative/unknown cancers in theoral cavity, oropharynx, hard palate, or tonsil (Group 3). RESULTS: 7/109 (6.4%) patients with HPV+ HNSCC developed DM. The median time to metastases was 11 months. At a median follow-up of 18-25 months, there was no difference in the overall rate of DM for the HPV+ HNSCC group compared to Group 2 (HPV-/unknown) (p = 0.21) and Group 3 (HPV-/unknown) (p = 0.13). There was a significant difference in the rate of DM to the lung in the HPV+ HNSCC group compared to Group 2 (HPV-/unknown) (p = 0.012) and Group 3 (HPV-/unknown) (p = 0.002). CONCLUSIONS: There was no observed difference in the time to development of DM between the HPV-/unknown and HPV+ HNSCC groups. However, the HPV+ HNSCC group showed a higher rate of DM to the lung compared to the HPV-/unknown -HNSCC group (p = 0.002).

Considerations of target surface area and the risk of radiosurgical toxicity.

OBJECTIVE: The goal of this study was to explore conceptual benefits of characterizing delineated target volumes based on surface area and to utilize the concept for assessing risk of therapeutic toxicity in radiosurgery. METHODS AND MATERIALS: Four computer-generated targets, a sphere, a cylinder, an ellipsoid and a box, were designed for two distinct scenarios. In the first scenario, all targets had identical volumes, and in the second one, all targets had identical surface areas. High quality stereotactic radiosurgery plans with at least 95% target coverage and selectivity were created for each target in both scenarios. Normal brain volumes V12Gy, V14Gy and V16Gy corresponding to received dose of 12 Gy, 14 Gy and 16 Gy, respectively, were computed and analyzed. Additionally, V12Gy and V14Gy volumes and values for seven prospective toxicity variables were recorded for 100 meningioma patients after Gamma Knife radiosurgery. Multivariable stepwise linear regression and best subset linear regression analyses were performed in two statistical software packages, SAS/STAT and R, respectively. RESULTS: In a phantom study, for the constant volume targets, the volumes of 12 Gy, 14 Gy and 16 Gy isodose clouds were the lowest for the spherical target as an expected corollary of the isoperimetric inequality. For the constant surface area targets, a conventional wisdom is confirmed, as the target volume increases the corresponding volumes V12Gy, V14Gy and V16Gy also increase. In the 100-meningioma patient cohort, the best univariate model featured tumor surface area as the most significantly associated variable with both V12Gy and V14Gy volumes, corresponding to the adjusted R2 values of 0.82 and 0.77, respectively. Two statistical methods converged to matching multivariable models. CONCLUSIONS: In a univariate model, target surface area is a better predictor of spilled dose to normal tissue than target largest dimension or target volume itself. In complex multivariate models, target surface area is an independent variable for modeling radiosurgical normal tissue toxicity risk.

Phase 1 Fractional Dose-Escalation Study of Equipotent Stereotactic Radiation Therapy Regimens for Early-Stage Glottic Larynx Cancer.

PURPOSE: Early-stage glottic larynx squamous cell carcinoma (GLC) is a relatively common disease with excellent oncologic control, but treatment is associated with acute dysphagia and long-term voice quality changes. This phase 1 study of hypofractionated radiation therapy for early-stage GLC increased the fraction size while reducing the number of fractions until 5-fraction stereotactic ablative radiation therapy (SABR) was delivered. METHODS AND MATERIALS: Eligible patients had received a diagnosis of stage Tis to T2 GLC. Patients who had undergone prior curative-intent surgery were excluded. The equipotent dose levels were as follows: (1) level 0, 50 Gy in 15 fractions (n = 4); (2) level 1, 45 Gy in 10 fractions (n = 13); and (3) level 2, 42.5 Gy in 5 fractions (SABR level, n = 12). Grade 3 or 4 laryngeal edema, voice, dyspnea, stridor, or cough were the predefined dose-limiting toxicities. RESULTS: Twenty-nine patients were enrolled from November 2013 to March 2017. The median and minimum follow-up times were 39.2 and 13 months, respectively. Two actively smoking patients, 1 treated in level 1 (grade 4 laryngeal edema, grade 3 dysphagia) and 1 treated in level 2 (grade 3 laryngeal necrosis, dysphagia), developed dose-limiting toxicities. The former patient soon developed a local recurrence, and the latter patient recovered. There were a total of 5 local recurrences: 2 in level 0 and 3 in level 1. The Voice Handicap Index results showed robust long-term voice quality with median values of 7 and 0 at 6 and 12 months, respectively. CONCLUSIONS: Given the tolerability, excellent voice outcomes, and preliminary efficacy data of 5-fraction glottic larynx SABR, this regimen warrants further study.

A Phase 2 Clinical Trial of SABR Followed by Immediate Vertebroplasty for Spine Metastases.

PURPOSE: To determine the pain response and prevention of vertebral compression fractures (VCFs) after single-fraction stereotactic ablative radiation therapy (SABR) in conjunction with immediate vertebroplasty for spine metastases. METHODS AND MATERIALS: Patients with localized spine metastases free from VCF associated with loss of vertebral height with a pain score ≥4 using the visual analog scale were enrolled. Spine SABR was performed with 20 Gy delivered to the gross disease and 14 Gy to the contiguous bone marrow in a single fraction. Immediate, prophylactic vertebroplasty was performed within 1 month after spine SABR. The primary endpoint was pain response at 3 months compared to the historical control with external beam radiation therapy from Radiation Therapy Oncology Group study 9714. Secondary endpoints included pain response at 1 month, duration of pain response, vertebroplasty rate, VCF rate, local control, and overall survival. RESULTS: Thirty-five patients were enrolled, of whom 29 were deemed eligible and underwent single-fraction spine SABR. Twenty-three of these patients subsequently underwent prophylactic vertebroplasty. The 3-month pain response was significantly improved compared to Radiation Therapy Oncology Group study 9714: 95% versus 51% (P < .0001). The local control with a median follow-up of 9.6 months was 92%. The freedom from VCF was 90% at 1 year. Spine SABR was well tolerated with no grade 2 or higher toxicities. A single patient with disease extending from the vertebral body into the spinal canal developed vertebroplasty-related myelopathy, which was corrected with surgery. CONCLUSIONS: Single-fraction SABR immediately followed by prophylactic vertebroplasty improves pain response compared with conventional radiation therapy while providing long-term pain control and structural stability of the treated spine. Vertebroplasty is well tolerated as a prophylactic measure in patients without loss of vertebral height after spine SABR. Pain response and VCF rates are similar to patients undergoing SABR alone. Thus, patients who would benefit most from the addition of vertebroplasty need to be further identified.

H3 K27M Mutations in Thalamic Pilocytic Astrocytomas with Anaplasia.

BACKGROUND: The revised World Health Organization classification of central nervous system tumors, published in 2016, has recognized the H3 K27M mutation as a critical genetic signature defining a new group of infiltrative astrocytomas designated as diffuse midline glioma, H3 K27M mutant. Although most H3 K27M mutations arise in the setting of diffusely infiltrative tumors, there are rare reports of compact tumors with low-grade histologic features harboring this mutation. The prevalence and clinical significance of this mutation in pilocytic astrocytomas remain unclear. CASE DESCRIPTION: We report 2 young adult patients with H3 K27M-mutated thalamic pilocytic astrocytomas who presented to medical attention with symptomatic hydrocephalus requiring urgent intervention. We present our experience with this unusual tumor and recommend a treatment paradigm of maximal safe surgical resection followed by chemotherapy and radiation. CONCLUSIONS: Stereotactic biopsies may undergrade some adult thalamic pilocytic astrocytomas. Therefore, we recommend that all these tumors be evaluated for the H3 K27M mutation. Further, we think H3 K27M-mutant thalamic pilocytic astrocytomas require aggressive multimodality treatment and these treatments should be guided by the molecular findings, as opposed to the histologic ones.

Stereotactic Radiosurgery for Multiple Brain Metastases From Renal-Cell Carcinoma.

BACKGROUND: Brain metastases (BM) pose a significant problem in patients with metastatic renal-cell carcinoma (mRCC). Local and systemic therapies including stereotactic radiosurgery (SRS) are rapidly evolving, necessitating reassessments of outcomes for modern patient management. PATIENTS AND METHODS: The mRCC patients with BM treated with SRS were reviewed. Patient demographics, clinical history, and SRS treatment parameters were identified. RESULTS: Among 268 patients with mRCC treated between 2006 and 2015, 38 patients were identified with BM. A total of 243 BM were treated with SRS with 1 to 26 BMs treated per SRS session (median, 2 BMs). The median (range) BM size was 0.6 (0.2-3.1) cm and median (range) SRS treatment dose was 18 (12-24) Gy. Treated BM local control rates at 1 and 2 years were 91.8% (95% confidence interval, 85.7-95.4) and 86.1% (95% confidence interval, 77.1-91.7), respectively. BM control declined for larger tumors. Survival after 1-year was 57.5% (95% CI 40.2-71.4) for all patients. Survival was not statistically different between patients with < 5 BM versus ≥ 5 BM. Survival was prognostic based on International Metastatic Renal Cell Carcinoma Database (IMDC) risk groups in patients with < 5 BM. Two patients experienced grade 3 radiation necrosis requiring surgical intervention. CONCLUSION: SRS is effective in controlling BM in patients with mRCC. Over half of treated patients survive past a year, and no differences in survival were noted in patients with > 5 metastases. Prognostic risk categories based on systemic disease (IMDC) are predictive of survival in this BM population, with limited rates of symptomatic radiation necrosis.

Risk of Unplanned Hospital Encounters in Patients Treated With Radiotherapy for Head and Neck Squamous Cell Carcinoma.

CONTEXT: Radiotherapy is highly effective for treating squamous cell carcinoma of the head and neck but is often associated with significant toxicities and severe morbidity. Unplanned emergency department (ED) visits and hospitalizations are common during treatment and come with a substantial financial and health burden as well as the potential for impaired long-term outcomes due to treatment disruption. OBJECTIVES: The objective of this study was to identify patient, disease, and treatment characteristics that were associated with ED encounters and admissions. METHODS: A cohort of 462 patients with cancer of the head and neck treated with radiotherapy at UT Southwestern between 2010 and 2015 was retrospectively analyzed. The risks of ED visits, admissions, multiple admissions, and extended admissions were determined. Risk factors for an unplanned hospital encounter were analyzed using univariate and multivariate logistic regression. RESULTS: Overall, 36% of patients had an unplanned hospital encounter during the treatment window. Patients with advanced disease, those with high comorbidity score, and those treated with concurrent chemotherapy were more likely to have unplanned admissions/ED visits. Social factors such as marital status, smoking status, and registration in the public hospital system were also strongly associated with admissions and multiple encounters. CONCLUSION: The high rate of admissions and ED visits emphasizes the importance of anticipating and managing toxicities during treatment. Social factors have a strong association with unplanned encounters and may present opportunities for targeted interventions to reduce admissions for patients at highest risk.

Head and neck neuroendocrine tumors at a single institution over 15 years.

Head and neck cancer is a diverse group of rare diseases such as neuroendocrine tumors which can be thought of as extrapulmonary small-cell cancer. Surgery, chemotherapy, and radiation can frequently cure this disease, possibly due to early detection.

A recursive ensemble organ segmentation (REOS) framework: application in brain radiotherapy.

The aim of this work is to develop a novel recursive ensemble OARs segmentation (REOS) framework for accurate organs-at-risk (OARs) automatic segmentation. The REOS recursively segment individual OARs by ensembling images features extracted from an organ localization module and a contour detection module. Both modules are based on a 3D U-Net architecture. The organ localization module is trained for rough segmentation to localize a region of interest (ROI) that encompasses the to-be-delineated OAR, while the contour detection module is trained to segment the OAR within the identified ROI. In this study, the developed REOS framework is applied for brain radiotherapy on segmenting six OARs including the eyes, the brainstem (BS), the optical nerves and the chiasm. Eighty T1-weighted magnetic resonance images (MRI) from 80 brain cancer patients' cases with OARs' gold standard contours were collected for training and testing REOS. On 20 testing cases, the REOS achieve a high segmentation accuracy with Dice similarity coefficient (DSC) mean and standard deviation of 93.9% ± 1.4%, 94.5% ± 2.0%, 90.6% ± 2.7%, on the left and right eyes and the BS, respectively. On small and segmentation-challenging organs, the left and right optical nerves and the chiasm, the REOS achieves DSC of 78.0% ± 10.5%, 82.2% ± 5.9% and 71.1% ± 9.1%. The satisfactory performances demonstrated the effectiveness of the REOS in OARs segmentation.

Association between treatment delays and oncologic outcome in patients treated with surgery and radiotherapy for head and neck cancer.

BACKGROUND: This study sought to determine the oncologic impact of delays to surgery, radiotherapy, and completion of therapy in patients with head and neck squamous cell carcinoma. METHODS: The impact of biopsy to surgery (BTS) time, surgery to start of radiation time (STSR), and radiation treatment time (RTT) on locoregional recurrence (LRR), distant metastases (DMs), and cancer-specific mortality (CSM) was examined. The cumulative incidences (CI) of LRR, DMs, and CSM were examined using Fine-Gray testing. RESULTS: A total of 277 patients treated with surgery and adjuvant radiotherapy were analyzed. On multivariable testing, BTS >50 days was associated with DM (P = .03), whereas RTT and STSR were not. RTT >43 days was associated with LRR (P = .02) in patients with non-p16-positive-oropharynx cancer. CONCLUSIONS: An increase in DM appears to be the mechanism by which prolonged time to treatment initiation leads to worse overall survival. Prolonged RTT has the greatest impact on patients with non-p16 positive oropharynx cancers.

Improved Survival Outcomes for Kidney Cancer Patients With Brain Metastases.

BACKGROUND: Brain metastases (BM) occur frequently in patients with metastatic kidney cancer and are a significant source of morbidity and mortality. Although historically associated with a poor prognosis, survival outcomes for patients in the modern era are incompletely characterized. In particular, outcomes after adjusting for systemic therapy administration and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factors are not well-known. PATIENTS AND METHODS: A retrospective database of patients with metastatic renal cell carcinoma (RCC) treated at University of Texas Southwestern Medical Center between 2006 and 2015 was created. Data relevant to their diagnosis, treatment course, and outcomes were systematically collected. Survival was analyzed by the Kaplan-Meier method. Patients with BM were compared with patients without BM after adjusting for the timing of BM diagnosis, either prior to or during first-line systemic therapy. The impact of stratification according to IMDC risk group was assessed. RESULTS: A total of 56 (28.4%) of 268 patients with metastatic RCC were diagnosed with BM prior to or during first-line systemic therapy. Median overall survival (OS) for systemic therapy-naive patients with BM compared with matched patients without BM was 19.5 versus 28.7 months (P = .0117). When analyzed according to IMDC risk group, the median OS for patients with BM was similar for favorable- and intermediate-risk patients (not reached vs. not reached; and 29.0 vs. 36.7 months; P = .5254), and inferior for poor-risk patients (3.5 vs. 9.4 months; P = .0462). For patients developing BM while on first-line systemic therapy, survival from the time of progression did not significantly differ by presence or absence of BM (11.8 vs. 17.8 months; P = .6658). CONCLUSIONS: Survival rates for patients with BM are significantly better than historical reports. After adjusting for systemic therapy, the survival rates of patients with BM in favorable- and intermediate-risk groups were remarkably better than expected and not statistically different from patients without BM, though this represents a single institution experience, and numbers are modest.

Neoadjuvant Stereotactic Radiosurgery Before Surgical Resection of Cerebral Metastases.

OBJECTIVE: Stereotactic radiosurgery (SRS) has redefined the treatment paradigm for cerebral metastases. The benefits of SRS after surgical resection of a metastatic brain tumor have been well-defined. However, it is unclear whether preoperative SRS can improve the outcomes in select patients. The present study examined the safety and efficacy of preoperative neoadjuvant SRS (NaSRS) for the treatment of cerebral metastases. METHODS: We performed a retrospective review of 12 patients treated at The University of Texas Southwestern Medical Center. All patients underwent NaSRS, followed by surgical resection of a cerebral metastasis, from 2011 to 2015. Recurrence and overall survival were characterized using Kaplan-Meier and log-rank analyses. RESULTS: The mean age was 57.5 years (range, 39-69). The median follow-up period was 13 months (range, 1-22.6). The median maximum tumor diameter was 3.66 cm (range, 2.19-4.85). The 6- and 12-month local control rates were 81.8% and 49.1%, respectively. The distant disease control rates were 72.7% and 14.5% at 6 and 12 months, respectively. Overall survival was 83.3% and 74.1% at 6 and 12 months, respectively. Two patients developed leptomeningeal disease at a mean of 11.3 months. A trend toward increased local failure was seen with larger tumor volumes and diameters (P = 0.06). CONCLUSIONS: NaSRS is a promising new approach for the treatment of select cerebral metastases that require surgical intervention. The approach is safe and effective at achieving local control. Further randomized studies with larger patient cohorts are necessary to determine whether the long-term outcomes are improved.

Stereotactic Body Radiation Therapy for Operable Early-Stage Lung Cancer: Findings From the NRG Oncology RTOG 0618 Trial.

Importance: Stereotactic body radiation therapy (SBRT) has become a standard treatment for patients with medically inoperable early-stage lung cancer. However, its effectiveness in patients medically suitable for surgery is unclear. Objective: To evaluate whether noninvasive SBRT delivered on an outpatient basis can safely eradicate lung cancer and cure selected patients with operable lung cancer, obviating the need for surgical resection. Design, Setting, and Participants: Single-arm phase 2 NRG Oncology Radiation Therapy Oncology Group 0618 study enrolled patients from December 2007 to May 2010 with median follow-up of 48.1 months (range, 15.4-73.7 months). The setting was a multicenter North American academic and community practice cancer center consortium. Patients had operable biopsy-proven peripheral T1 to T2, N0, M0 non-small cell tumors no more than 5 cm in diameter, forced expiratory volume in 1 second (FEV1) and diffusing capacity greater than 35% predicted, arterial oxygen tension greater than 60 mm Hg, arterial carbon dioxide tension less than 50 mm Hg, and no severe medical problems. The data analysis was performed in October 2014. Interventions: The SBRT prescription dose was 54 Gy delivered in 3 18-Gy fractions over 1.5 to 2.0 weeks. Main Outcomes and Measures: Primary end point was primary tumor control, with survival, adverse events, and the incidence and outcome of surgical salvage as secondary end points. Results: Of 33 patients accrued, 26 were evaluable (23 T1 and 3 T2 tumors; 15 [58%] male; median age, 72.5 [range, 54-88] years). Median FEV1 and diffusing capacity of the lung for carbon monoxide at enrollment were 72.5% (range, 38%-136%) and 68% (range, 22%-96%) of predicted, respectively. Only 1 patient had a primary tumor recurrence. Involved lobe failure, the other component defining local failure, did not occur in any patient, so the estimated 4-year primary tumor control and local control rate were both 96% (95% CI, 83%-100%). As per protocol guidelines, the single patient with local recurrence underwent salvage lobectomy 1.2 years after SBRT, complicated by a grade 4 cardiac arrhythmia. The 4-year estimates of disease-free and overall survival were 57% (95% CI, 36%-74%) and 56% (95% CI, 35%-73%), respectively. Median overall survival was 55.2 months (95% CI, 37.7 months to not reached). Protocol-specified treatment-related grade 3, 4, and 5 adverse events were reported in 2 (8%; 95% CI, 0.1%-25%), 0, and 0 patients, respectively. Conclusions and Relevance: As given, SBRT appears to be associated with a high rate of primary tumor control, low treatment-related morbidity, and infrequent need for surgical salvage in patients with operable early-stage lung cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT00551369.