Publications by authors named "John H Suh"

213 Publications

A Volumetric Dosimetry Analysis of Vertebral Body Fracture Risk after Single Fraction Spine Stereotactic Body Radiotherapy.

Pract Radiat Oncol 2021 Jul 22. Epub 2021 Jul 22.

Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH. Electronic address:

Purpose: Vertebral compression fractures (VCF) are a common and severe complication of spine stereotactic body radiotherapy (SBRT). We sought to analyze how volumetric dosimetry and clinical factors were associated with the risk of VCF.

Methods And Materials: We evaluated 173 spinal segments undergoing single fraction SBRT in 85 patients from a retrospective database. Vertebral bodies were contoured and dosimetric values were calculated. Competing risk models were used to evaluate the effect of clinical and dosimetry variables on the risk of VCF.

Results: Our primary endpoint was development of a post SBRT VCF. New or progressive fractures were noted in 21/173 vertebrae (12.1%); the median time to fracture was 322 days. Median follow up time was 426 days. Upon multivariable analysis, the percentages of vertebral body volume receiving >20 Gy and >24 Gy were significantly associated with increased risk of VCF (HR: 1.036, 1.104; p = 0.029, 0.044 respectively). No other patient or treatment factors were found to be significant on multivariable analysis. Sensitivity analysis revealed that the percentages of vertebral body volume receiving >20 Gy and >24 Gy required to obtain 90% sensitivity for predicting vertebral body fracture were 24% and 0%, respectively.

Conclusions: VCF is a common complication after SBRT with a crude incidence of 12.1%. Treatment plans that permit higher volumes receiving doses >20 Gy and >24 Gy to the vertebral body are associated with increased risk of VCF. In order to achieve 90% sensitivity for predicting VCF post SBRT, the percentage of vertebral volume receiving >20 Gy should be <24% and maximum point dose should be <24 Gy. These results may help guide clinicians when evaluating spine SBRT treatment plans to minimize the risk of developing post-treatment VCF.
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http://dx.doi.org/10.1016/j.prro.2021.07.004DOI Listing
July 2021

Radiation Necrosis from Stereotactic Radiosurgery-How Do We Mitigate?

Curr Treat Options Oncol 2021 Jun 7;22(7):57. Epub 2021 Jun 7.

Department of Radiation Oncology, University of Washington School of Medicine, Seattle, WA, USA.

Opinion Statement: Intracranial stereotactic radiosurgery (SRS) is an effective and convenient treatment for many brain conditions. Data regarding safety come mostly from retrospective single institutional studies and a small number of prospective studies. Variations in target delineation, treatment delivery, imaging follow-up protocols and dose prescription limit the interpretation of this data. There has been much clinical focus on radiation necrosis (RN) in particular, as it is being increasingly recognized on follow-up imaging. Symptomatic RN may be treated with medical therapy (such as corticosteroids and bevacizumab) with surgical resection being reserved for refractory patients. Nevertheless, RN remains a challenging condition to manage, and therefore upfront patient selection for SRS remains critical to provide complication-free control. Mitigation strategies need to be considered in situations where the baseline risk of RN is expected to be high-such as large target volume or re-irradiation. These may involve reduction in the prescribed dose or hypofractionated stereotactic radiation therapy (HSRT). Recently published guidelines and international meta-analysis report the benefit of HSRT in larger lesions, without compromising control rates. However, careful attention to planning parameters and SRS techniques still need to be adhered, even with HSRT. In cases where the risk is deemed to be high despite mitigation, a combination approach of surgery with or without post-operative radiation should be considered.
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http://dx.doi.org/10.1007/s11864-021-00854-zDOI Listing
June 2021

Outcomes of salvage radiation for recurrent world health organization grade II meningiomas: a retrospective cohort study.

J Neurooncol 2021 Apr 15;152(2):373-382. Epub 2021 Feb 15.

Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA.

Purpose: The optimal modality of radiation-intensity-modulated radiation therapy (IMRT) or stereotactic radiosurgery (SRS)-in patients with recurrent WHO grade II meningiomas is not well-established. The purpose of this study was to compare progression-free survival (PFS) in patients undergoing salvage IMRT vs SRS. We compared PFS in those with and without history of prior radiation.

Methods: Forty-two patients with 71 tumor recurrences treated with IMRT or SRS were retrospectively reviewed. Thirty-two salvage treatments were performed on recurrent tumors never treated with prior radiation ('radiation-naïve' cohort), whereas 39 salvage treatments were performed on recurrent tumors previously treated with radiation ('re-treatment cohort').

Results: In the 'radiation-naïve' cohort, 3-year PFS for IMRT and SRS was 68.8% and 60.7%, respectively (p = 0.61). The median tumor volume for patients treated with IMRT was significantly larger than for patients treated with SRS (5.7 vs 2.2 cm; p = 0.04). The 3-year PFS for salvage IMRT or SRS in the 're-treatment' cohort was 45.4% vs 65.8% in the 'radiation-naïve' cohort (p = 0.008). When analyzing the outcome of multiple re-treatments, median PFS was 47 months for 1 or 2nd salvage radiation (IMRT or SRS) compared to 16 months for the 3rd or greater salvage radiation treatment (p = 0.003).

Conclusion: For salvage radiation of recurrent grade II tumors that are 'radiation-naïve', comparable 3-year PFS rates were found between IMRT and SRS, despite the IMRT group having significantly larger tumors. Salvage radiation overall was less successful in the 're-treatment' cohort compared with the 'radiation-naïve' cohort. Additionally, the effectiveness of radiation significantly declines with successive salvage radiation treatments.
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http://dx.doi.org/10.1007/s11060-021-03711-zDOI Listing
April 2021

The Judicious Use of Stereotactic Radiosurgery and Hypofractionated Stereotactic Radiotherapy in the Management of Large Brain Metastases.

Cancers (Basel) 2020 Dec 29;13(1). Epub 2020 Dec 29.

Department of Radiation Oncology, University of Washington School of Medicine, Seattle, WA 98195, USA.

Brain metastases are the most common intracranial malignant tumor in adults and are a cause of significant morbidity and mortality for cancer patients. Large brain metastases, defined as tumors with a maximum dimension >2 cm, present a unique clinical challenge for the delivery of stereotactic radiosurgery (SRS) as patients often present with neurologic symptoms that require expeditious treatment that must also be balanced against the potential consequences of surgery and radiation therapy-namely, leptomeningeal disease (LMD) and radionecrosis (RN). Hypofractionated stereotactic radiotherapy (HSRT) and pre-operative SRS have emerged as novel treatment techniques to help improve local control rates and reduce rates of RN and LMD for this patient population commonly managed with post-operative SRS. Recent literature suggests that pre-operative SRS can potentially half the risk of LMD compared to post-operative SRS and that HSRT can improve risk of RN to less than 10% while improving local control when meeting the appropriate goals for biologically effective dose (BED) and dose-volume constraints. We recommend a 3- or 5-fraction regimen in lieu of SRS delivering 15 Gy or less for large metastases or resection cavities. We provide a table comparing the BED of commonly used SRS and HSRT regimens, and provide an algorithm to help guide the management of these challenging clinical scenarios.
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http://dx.doi.org/10.3390/cancers13010070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795798PMC
December 2020

Typically, We Would Observe.

Int J Radiat Oncol Biol Phys 2020 11;108(3):520

Cleveland Clinic, Taussig Cancer Institute, Department of Radiation Oncology, Cleveland, Ohio; Rose Ella Burkhardt Tumor and Neuro-Oncology Center, Cleveland, Ohio.

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http://dx.doi.org/10.1016/j.ijrobp.2019.07.020DOI Listing
November 2020

Analysis of cardiac motion without respiratory motion for cardiac stereotactic body radiation therapy.

J Appl Clin Med Phys 2020 Oct 12;21(10):48-55. Epub 2020 Sep 12.

Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.

Purpose/objective(s): To study the heart motion using cardiac gated computed tomographies (CGCT) to provide guidance on treatment planning margins during cardiac stereotactic body radiation therapy (SBRT).

Materials/methods: Ten patients were selected for this study, who received CGCT scans that were acquired with intravenous contrast under a voluntary breath-hold using a dual source CT scanner. For each patient, CGCT images were reconstructed in multiple phases (10%-90%) of the cardiac cycle and the left ventricle (LV), right ventricle (RV), ascending aorta (AAo), ostia of the right coronary artery (O-RCA), left coronary artery (O-LCA), and left anterior descending artery (LAD) were contoured at each phase. For these contours, the centroid displacements from their corresponding average positions were measured at each phase in the superior-inferior (SI), medial-lateral (ML), and anterior-posterior (AP). The average volumes as well as the maximum to minimum ratios were analyzed for the LV and RV.

Results: For the six contoured substructures, more than 90% of the measured displacements were <5 mm. For these patients, the average volumes ranged from 191.25 to 429.51 cc for LV and from 91.76 to 286.88 cc for RV. For each patient, the ratios of maximum to minimum volumes within a cardiac cycle ranged from 1.15 to 1.54 for LV and from 1.34 to 1.84 for RV.

Conclusion: Based on this study, cardiac motion is variable depending on the specific substructure of the heart but is mostly within 5 mm. Depending on the location (central or peripheral) of the treatment target and treatment purposes, the treatment planning margins for targets and risk volumes should be adjusted accordingly. In the future, we will further assess heart motion and its dosimetric impact.
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http://dx.doi.org/10.1002/acm2.13002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592981PMC
October 2020

Combining automatic plan integrity check (APIC) with standard plan document and checklist method to reduce errors in treatment planning.

J Appl Clin Med Phys 2020 Sep 17;21(9):124-133. Epub 2020 Jul 17.

Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.

Purpose/objectives: To report our experience of combining three approaches of an automatic plan integrity check (APIC), a standard plan documentation, and checklist methods to minimize errors in the treatment planning process.

Materials/methods: We developed APIC program and standardized plan documentation via scripting in the treatment planning system, with an enforce function of APIC usage. We used a checklist method to check for communication errors in patient charts (referred to as chart errors). Any errors in the plans and charts (referred to as the planning errors) discovered during the initial chart check by the therapists were reported to our institutional Workflow Enhancement (WE) system. Clinical Implementation of these three methods is a progressive process while the APIC was the major progress among the three methods. Thus, we chose to compared the total number of planning errors before (including data from 2013 to 2014) and after (including data from 2015 to 2018) APIC implementation. We assigned the severity of these errors into five categories: serious (S), near miss with safety net (NM), clinical interruption (CLI), minor impediment (MI), and bookkeeping (BK). The Mann-Whitney U test was used for statistical analysis.

Results: A total of 253 planning error forms, containing 272 errors, were submitted during the study period, representing an error rate of 3.8%, 3.1%, 2.1%, 0.8%, 1.9% and 1.3% of total number of plans in these years respectively. A marked reduction of planning error rate in the S and NM categories was statistically significant (P < 0.01): from 0.6% before APIC to 0.1% after APIC. The error rate for all categories was also significantly reduced (P < 0.01), from 3.4% before APIC and 1.5% per plan after APIC.

Conclusion: With three combined methods, we reduced both the number and the severity of errors significantly in the process of treatment planning.
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http://dx.doi.org/10.1002/acm2.12981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497915PMC
September 2020

Stereotactic Radiosurgery for Intracranial Noncavernous Sinus Benign Meningioma: International Stereotactic Radiosurgery Society Systematic Review, Meta-Analysis and Practice Guideline.

Neurosurgery 2020 10;87(5):879-890

Department of Neurosurgery, Unit of Radiotherapy, Fondazione IRCCS Istituto Neurologico C. Besta, Milano, Italia.

Background: Stereotactic radiosurgery (SRS) for benign intracranial meningiomas is an established treatment.

Objective: To summarize the literature and provide evidence-based practice guidelines on behalf of the International Stereotactic Radiosurgery Society (ISRS).

Methods: Articles in English specific to SRS for benign intracranial meningioma, published from January 1964 to April 2018, were systematically reviewed. Three electronic databases, PubMed, EMBASE, and the Cochrane Central Register, were searched.

Results: Out of the 2844 studies identified, 305 had a full text evaluation and 27 studies met the criteria to be included in this analysis. All but one were retrospective studies. The 10-yr local control (LC) rate ranged from 71% to 100%. The 10-yr progression-free-survival rate ranged from 55% to 97%. The prescription dose ranged typically between 12 and 15 Gy, delivered in a single fraction. Toxicity rate was generally low.

Conclusion: The current literature supporting SRS for benign intracranial meningioma lacks level I and II evidence. However, when summarizing the large number of level III studies, it is clear that SRS can be recommended as an effective evidence-based treatment option (recommendation level II) for grade 1 meningioma.
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http://dx.doi.org/10.1093/neuros/nyaa169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566438PMC
October 2020

Commentary: Mature Imaging-Based Outcomes Supporting Local Control for Complex Reirradiation Salvage Spine Stereotactic Body Radiotherapy.

Neurosurgery 2020 09;87(4):E498-E499

Department of Neurological Surgery, University of Washington School of Medicine, Seattle, Washington.

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http://dx.doi.org/10.1093/neuros/nyaa159DOI Listing
September 2020

Neuro-oncology Management During the COVID-19 Pandemic With a Focus on WHO Grade III and IV Gliomas.

Neuro Oncol 2020 May 5. Epub 2020 May 5.

Technical University of Munich (TUM), School of Medicine and Klinikum rechts der Isar, Department of Radiation Oncology, Munich.

Background: Because of the increased risk in cancer patients of developing complications caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), physicians have to balance the competing risks of the negative impact of the pandemic and the primary tumor. In this consensus statement, an international group of experts present mitigation strategies and treatment guidance for patients suffering from high grade gliomas (HGG) during the coronavirus disease 2019 (COVID-19) pandemic.

Method / Results: 16 international experts in the treatment of HGG contributed to this consensus-based practice recommendation including neuro-oncologists, neurosurgeons, radiation -oncologists and a medical physicist. Generally, treatment of neuro-oncological patients cannot be significantly delayed and initiating therapy should not be outweighed by COVID-19. We present detailed interdisciplinary treatment strategies for molecular subgroups in two pandemic scenarios, a scale-up phase and a crisis phase.

Conclusion: This practice recommendation presents a pragmatic framework and consensus-based mitigation strategies for the treatment of HGG patients during the SARS-CoV-2 pandemic.
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http://dx.doi.org/10.1093/neuonc/noaa113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239150PMC
May 2020

Analyzing the role of adjuvant or salvage radiotherapy for spinal myxopapillary ependymomas.

J Neurosurg Spine 2020 May 1:1-6. Epub 2020 May 1.

3Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic; and Departments of.

Objective: The authors sought to describe the long-term recurrence patterns, prognostic factors, and effect of adjuvant or salvage radiotherapy (RT) on treatment outcomes for patients with spinal myxopapillary ependymoma (MPE).

Methods: The authors reviewed a tertiary institution IRB-approved database and collected data regarding patient, tumor, and treatment characteristics for all patients treated consecutively from 1974 to 2015 for histologically confirmed spinal MPE. Key outcomes included relapse-free survival (RFS), postrecurrence RFS, failure patterns, and influence of timing of RT on recurrence patterns. Cox proportional hazards regression and Kaplan-Meier analyses were utilized.

Results: Of the 59 patients included in the study, the median age at initial surgery was 34 years (range 12-74 years), 30 patients (51%) were female, and the most common presenting symptom was pain (n = 52, 88%). Extent of resection at diagnosis was gross-total resection (GTR) in 39 patients (66%), subtotal resection (STR) in 15 (25%), and unknown in 5 patients (9%). After surgery, 10 patients (17%) underwent adjuvant RT (5/39 GTR [13%] and 5/15 STR [33%] patients). Median follow-up was 6.2 years (range 0.1-35.3 years). Overall, 20 patients (34%) experienced recurrence (local, n = 15; distant, n = 5). The median RFS was 11.2 years (95% CI 77 to not reached), and the 5- and 10-year RFS rates were 72.3% (95% CI 59.4-86.3) and 54.0% (95% CI, 36.4-71.6), respectively.STR was associated with a higher risk of recurrence (HR 6.45, 95% CI 2.15-19.23, p < 0.001) than GTR, and the median RFS after GTR was 17.2 years versus 5.5 years after STR. Adjuvant RT was not associated with improved RFS, regardless of whether it was delivered after GTR or STR. Of the 20 patients with recurrence, 12 (60%) underwent salvage treatment with surgery alone (GTR, n = 6), 4 (20%) with RT alone, and 4 (20%) with surgery and RT. Compared to salvage surgery alone, salvage RT, with or without surgery, was associated with a significantly longer postrecurrence RFS (median 9.5 years vs 1.6 years; log-rank, p = 0.006).

Conclusions: At initial diagnosis of spinal MPE, GTR is key to long-term RFS, with no benefit to immediate adjuvant RT observed in this series. RT at the time of recurrence, however, is associated with a significantly longer time to second disease recurrence. Surveillance imaging of the entire neuraxis remains crucial, as distant failure is not uncommon in this patient population.
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http://dx.doi.org/10.3171/2020.2.SPINE191534DOI Listing
May 2020

Marital Status and Overall Survival in Patients with Resectable Pancreatic Cancer: Results of an Ancillary Analysis of NRG Oncology/RTOG 9704.

Oncologist 2020 03 16;25(3):e477-e483. Epub 2019 Dec 16.

Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Background: Several registry-based analyses suggested a survival advantage for married versus single patients with pancreatic cancer. The mechanisms underlying the association of marital status and survival are likely multiple and complex and, therefore, may be obscured in analyses generated from large population-based databases. The goal of this research was to characterize this potential association of marital status with outcomes in patients with resected pancreatic cancer who underwent combined modality adjuvant therapy on a prospective clinical trial.

Materials And Methods: This is an ancillary analysis of 367 patients with known marital status treated on NRG Oncology/RTOG 97-04. Survival analysis was performed using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis was performed using the Cox proportional hazards regression model.

Results: Of 367 patients, 271 (74%) were married or partnered and 96 (26%) were single. Married or partnered patients were more likely to be male. There was no association between marital status and overall survival (OS) or disease-free survival (DFS) on univariate (hazard ratio [HR], 1.09 and 1.01, respectively) or multivariate analyses (HR, 1.05 and 0.98, respectively). Married or partnered male patients did not have improved survival compared with female or single patients.

Conclusion: Ancillary analysis of data from NRG Oncology/RTOG 97-04 demonstrated no association between marital and/or partner status and OS or DFS in patients with resected pancreatic cancer who received adjuvant postoperative chemotherapy followed by concurrent external beam radiation therapy and chemotherapy. Clinical trial identification number. NCT00003216.

Implications For Practice: Several population-based studies have shown an epidemiological link between marital status and survival in patients with pancreatic cancer. A better understanding of this association could offer an opportunity to improve outcomes through psychosocial interventions designed to mitigate the negative effects of not being married. Based on the results of this analysis, patients who have undergone a resection and are receiving adjuvant therapy on a clinical trial are unlikely to benefit from such interventions. Further efforts to study the association between marital status and survival should be focused on less selected subgroups of patients with pancreatic cancer.
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http://dx.doi.org/10.1634/theoncologist.2019-0562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066692PMC
March 2020

Current approaches to the management of brain metastases.

Nat Rev Clin Oncol 2020 05 20;17(5):279-299. Epub 2020 Feb 20.

Department of Radiation Oncology, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.

Brain metastases are a very common manifestation of cancer that have historically been approached as a single disease entity given the uniform association with poor clinical outcomes. Fortunately, our understanding of the biology and molecular underpinnings of brain metastases has greatly improved, resulting in more sophisticated prognostic models and multiple patient-related and disease-specific treatment paradigms. In addition, the therapeutic armamentarium has expanded from whole-brain radiotherapy and surgery to include stereotactic radiosurgery, targeted therapies and immunotherapies, which are often used sequentially or in combination. Advances in neuroimaging have provided additional opportunities to accurately screen for intracranial disease at initial cancer diagnosis, target intracranial lesions with precision during treatment and help differentiate the effects of treatment from disease progression by incorporating functional imaging. Given the numerous available treatment options for patients with brain metastases, a multidisciplinary approach is strongly recommended to personalize the treatment of each patient in an effort to improve the therapeutic ratio. Given the ongoing controversies regarding the optimal sequencing of the available and expanding treatment options for patients with brain metastases, enrolment in clinical trials is essential to advance our understanding of this complex and common disease. In this Review, we describe the key features of diagnosis, risk stratification and modern paradigms in the treatment and management of patients with brain metastases and provide speculation on future research directions.
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http://dx.doi.org/10.1038/s41571-019-0320-3DOI Listing
May 2020

The effect of Gamma Knife radiosurgery on large posterior fossa metastases and the associated mass effect from peritumoral edema.

J Neurosurg 2020 Jan 24:1-9. Epub 2020 Jan 24.

1Department of Neurosurgery, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland Clinic, Cleveland.

Objective: Gamma Knife radiosurgery (GKRS) as monotherapy is an option for the treatment of large (≥ 2 cm) posterior fossa brain metastases (LPFMs). However, there is concern regarding possible posttreatment increase in peritumoral edema (PTE) and associated compression of the fourth ventricle. This study evaluated the effects and safety of GKRS on tumor and PTE control in LPFM.

Methods: The authors performed a single-center retrospective review of 49 patients with 51 LPFMs treated with GKRS. Patients with at least 1 clinical and radiological follow-up visit were included. Tumor, PTE, and fourth ventricle volumetric measurements were used to assess efficacy and safety. Overall survival was a secondary outcome.

Results: Fifty-one lesions in 49 consecutive patients were identified; 57.1% of patients were male. At the time of GKRS, the median age was 61.5 years, and the median Karnofsky Performance Status score was 90. The median number of LPFMs and overall brain metastases were 1 and 2, respectively. The median overall tumor, PTE, and fourth ventricle volumes at diagnosis were 4.96 cm3 (range 1.4-21.1 cm3), 14.98 cm3 (range 0.6-71.8 cm3), and 1.23 cm3 (range 0.3-3.2 cm3), respectively, and the median lesion diameter was 2.6 cm (range 2.0-5.07 cm). The median follow-up time was 7.3 months (range 1.6-57.2 months). At the first follow-up, 2 months posttreatment, the median tumor volume decreased by 58.66% (range -96.95% to +48.69%, p < 0.001), median PTE decreased by 78.10% (range -99.92% to +198.35%, p < 0.001), and the fourth ventricle increased by 24.97% (range -37.96% to +545.6%, p < 0.001). The local control rate at first follow-up was 98.1%. The median OS was 8.36 months. No patient required surgical intervention, external ventricular drainage, or shunting between treatment and first follow-up. However, 1 patient required a ventriculoperitoneal shunt at 23 months from treatment. Posttreatment, 65.30% received our general steroid taper, 6.12% received no steroids, and 28.58% required prolonged steroid treatment.

Conclusions: In this retrospective analysis, patients with LPFMs treated with GKRS had a statistically significant posttreatment reduction in tumor size and PTE and marked opening of the fourth ventricle (all p < 0.001). This study demonstrates that GKRS is well tolerated and can be considered in the management of select cases of LPFMs, especially in patients who are poor surgical candidates.
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http://dx.doi.org/10.3171/2019.11.JNS191485DOI Listing
January 2020

Treatment planning of VMAT and step-and-shoot IMRT delivery techniques for single fraction spine SBRT: An intercomparative dosimetric analysis and phantom-based quality assurance measurements.

J Appl Clin Med Phys 2020 Jan 10;21(1):62-68. Epub 2019 Dec 10.

Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.

Purpose: To retrospectively compare clinically treated step-and-shoot intensity modulated radiotherapy (ssIMRT) and volumetric modulated arc therapy (VMAT) spine stereotactic body radiotherapy (SBRT) plans in dosimetric endpoints and pretreatment quality assurance (QA) measurements.

Methods: Five single fraction spine SBRT (18 Gy) cases - including one cervical, two thoracic, and two lumbar spines - clinically treated with ssIMRT were replanned with VMAT, and all plans were delivered to a phantom for comparing plan quality and delivery accuracy. Furthermore, we analyzed 98 clinically treated plans (18 Gy single fraction), including 34 ssIMRT and 29 VMAT for cervical/thoracic spine, and 19 ssIMRT and 16 VMAT for lumbar spine. The conformality index (CI) and homogeneity index (HI) were calculated, and QA measurement records were compared. For the spinal cord/cauda equina, the maximum dose to 0.03 cc (D ) and volume receiving 10 or 12 Gy (V /V ) were recorded. Statistical significance was tested with the Mann-Whitney U test.

Results: Compared to ssIMRT, replanned VMAT plans had lower V /V and D to the spinal cord/cauda equina in all five cases, and better CI in three out of five cases. The VMAT replans were slightly less homogeneous than those of ssIMRT plans. Both modalities passed IMRT QA with >95% passing rate with (3%, 3 mm) gamma criteria. With the 98 clinical cases, for cervical/thoracic ssIMRT and VMAT plans, the median V of spinal cord was 4.15% and 1.85% (P = 0.004); the median D of spinal cord was 10.85 Gy and 10.10 Gy (P = 0.032); the median CI was 1.28 and 1.08 (P = 0.009); the median HI were 1.34 and 1.33 (P = 0.697), respectively. For lumbar spine, no significant dosimetric endpoint differences were observed. The two modalities were comparable in delivery accuracy.

Conclusion: From our clinically treated plans, we found that VMAT plans provided better dosimetric quality and comparable delivery accuracy when compared to ssIMRT for single fraction spine SBRT.
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http://dx.doi.org/10.1002/acm2.12788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964769PMC
January 2020

Stereotactic radiosurgery for non-functioning pituitary adenomas: meta-analysis and International Stereotactic Radiosurgery Society practice opinion.

Neuro Oncol 2020 03;22(3):318-332

Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA.

Background: This systematic review reports on outcomes and toxicities following stereotactic radiosurgery (SRS) for non-functioning pituitary adenomas (NFAs) and presents consensus opinions regarding appropriate patient management.

Methods: Using the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, a systematic review was performed from articles of ≥10 patients with NFAs published prior to May 2018 from the Medline database using the key words "radiosurgery" and "pituitary" and/or "adenoma." Weighted random effects models were used to calculate pooled outcome estimates.

Results: Of the 678 abstracts reviewed, 35 full-text articles were included describing the outcomes of 2671 patients treated between 1971 and 2017 with either single fraction SRS or hypofractionated stereotactic radiotherapy (HSRT). All studies were retrospective (level IV evidence). SRS was used in 27 studies (median dose: 15 Gy, range: 5-35 Gy) and HSRT in 8 studies (median total dose: 21 Gy, range: 12-25 Gy, delivered in 3-5 fractions). The 5-year random effects local control estimate after SRS was 94% (95% CI: 93.0-96.0%) and 97.0% (95% CI: 93.0-98.0%) after HSRT. The 10-year local control random effects estimate after SRS was 83.0% (95% CI: 77.0-88.0%). Post-SRS hypopituitarism was the most common treatment-related toxicity observed, with a random effects estimate of 21.0% (95% CI: 15.0-27.0%), whereas visual dysfunction or other cranial nerve injuries were uncommon (range: 0-7%).

Conclusions: SRS is an effective and safe treatment for patients with NFAs. Encouraging short-term data support HSRT for select patients, and mature outcomes are needed before definitive recommendations can be made. Clinical practice opinions were developed on behalf of the International Stereotactic Radiosurgery Society (ISRS).
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http://dx.doi.org/10.1093/neuonc/noz225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058447PMC
March 2020

Spine radiosurgery in adolescents and young adults: early outcomes and toxicity in patients with metastatic Ewing sarcoma and osteosarcoma.

J Neurosurg Spine 2019 Nov 29:1-8. Epub 2019 Nov 29.

1Department of Radiation Oncology, Taussig Cancer Institute.

Objective: There are limited data on spine stereotactic radiosurgery (SRS) in treating adolescent and young adult (AYA) patients. SRS has the advantages of highly conformal radiation dose delivery in the upfront and retreatment settings, means for dose intensification, and administration over a limited number of sessions leading to a decreased treatment burden. In this study, the authors report the oncological and toxicity outcomes for AYA patients with metastatic sarcoma treated with spine radiosurgery and provide clinicians a guide for considerations in dose, volume, and fractionation.

Methods: An institutional review board-approved database of patients treated with SRS in the period from October 2014 through December 2018 was queried. AYA patients, defined by ages 15-29 years, who had been treated with SRS for spine metastases from Ewing sarcoma or osteosarcoma were included in this analysis. Patients with follow-ups shorter than 6 months after SRS were excluded. Local control, overall survival, and toxicity were reported.

Results: Seven patients with a total of 11 treated lesions were included in this study. Median patient age was 20.3 years (range 15.1-26.1 years). Three patients had Ewing sarcoma (6 lesions) and 4 patients had osteosarcoma (5 lesions). The median dose delivered was 35 Gy in 5 fractions (range 16-40 Gy, 1-5 fractions). The median follow-up was 11.1 months (range 6.8-26.0 months). Three local failures were observed within the follow-up period. No acute grade 3 or greater toxicity was observed. One patient developed late grade 3 toxicity consisting of radiation enteritis. This patient had previously received radiation to an overlapping volume with conventional fractionation. SRS re-irradiation for this patient was also performed concurrently with chemotherapy administration. No late grade 4 or higher toxicities were observed. No pain flare or vertebral compression fracture was observed. Three patients died within the follow-up period.

Conclusions: SRS for spine metastases from Ewing sarcoma and osteosarcoma can be considered as a treatment option in AYA patients and is associated with acceptable toxicity rates. Further studies must be conducted to determine long-term local control and toxicity for this treatment modality.
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http://dx.doi.org/10.3171/2019.9.SPINE19377DOI Listing
November 2019

Pathologic Correlation of Cellular Imaging Using Apparent Diffusion Coefficient Quantification in Patients with Brain Metastases After Gamma Knife Radiosurgery.

World Neurosurg 2020 Feb 13;134:e903-e912. Epub 2019 Nov 13.

Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio, USA; Rose Ella Burkhart Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, Ohio, USA. Electronic address:

Objective: To evaluate the role of apparent diffusion coefficient (ADC) in differentiating radiation necrosis (RN) from recurrent tumor after Gamma Knife radiosurgery (GKRS) for brain metastases (BMs).

Methods: Forty-one patients with BM who underwent surgical intervention after GKRS at Cleveland Clinic (2006-2017) were included in this retrospective study. The ADC values of the growing lesions and the contralateral hemisphere were calculated using picture archiving and communication system. These values were correlated to the percentage of RN identified on pathologic evaluation of the surgical specimen.

Results: The median age of the patients was 59 years (range, 25-86 years), and lung cancer (63.4%) was the most common malignancy. Median initial (pre-GKRS) target volume of the lesions was 5.4 cc (range, 0.135-45.6 cc), and median GKRS dose was 18.0 Gy. Surgical resection or biopsy was performed at a median of 176 days after GKRS. Two variables were statistically significant predictors of predominate RN (75%-100%) in the surgical specimen: 1) ADC of the lesion on the preresection magnetic resonance imaging (MRI) and 2) initial pre-GKRS target volume. ADC >1.5 × 10 mm/s within the lesion on MRI predicted significant RN on pathologic evaluation of the lesion (P < 0.05). Similarly, when the target volume before GKRS was large (>10 cc), the risk of identifying significant necrosis in the pathologic specimen was elevated (P < 0.05).

Conclusions: Our data suggest that the combination of lesion ADC on MRI prior to surgical intervention and the initial target volume can predict RN with reasonable accuracy.
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http://dx.doi.org/10.1016/j.wneu.2019.11.037DOI Listing
February 2020

Impact of EGFR mutation and ALK rearrangement on the outcomes of non-small cell lung cancer patients with brain metastasis.

Neuro Oncol 2020 02;22(2):267-277

Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, Ohio.

Background: The impact of activating alterations in non-small cell lung cancer (NSCLC) (epidermal growth factor receptor [EGFR] mutation/anaplastic lymphoma kinase [ALK] translocation) in prognosticating patients with brain metastasis (BM) is not well defined. This study was sought to identify this impact in NSCLC patients with BM accounting for the known validated variables.

Methods: Among 1078 NSCLC-BM patients diagnosed/treated between January 1, 2000 and December 31, 2015, three hundred and forty-eight with known EGFR/ALK status were analyzed. Overall survival (OS) and intracranial progression-free survival (PFS) were measured from the time of BM.

Results: Ninety-one patients had either ALK (n = 23) alterations or EGFR (n = 68) mutation and 257 were wild type (WT; negative actionable mutations/alterations). Median age of EGFR/ALK+ NSCLC BM patients was 60 years (range 29.8-82.6 y) and ~50% (n = 44) had Karnofsky performance status (KPS) score >80. Median number of BM was 2 (1 to ≥99). The median OS for the ALK/EGFR+ NSCLC BM was 19.9 versus 10.1 months for the WT (P = 0.028). The number of BM in the EGFR/ALK+ group did not impact OS (BM = 1 with 21.1 months vs 2-3 with 19.1 months and >3 with 23.7 months, P = 0.74), whereas fewer BM in the WT cohort had significantly better OS (BM = 1 with 13.8 mo, 2-3 with 11.0 mo and >3 with 8.1 mo; P = 0.006) with the adjustment of age, KPS, symptoms from BM and synchronicity.

Conclusions: Number of BM does not impact outcomes in the EGFR/ALK+ NSCLC patients, implying that targeted therapy along with surgery and/or radiation may improve OS irrespective of the number of BM. Number of BM, extracranial metastasis (ECM), and KPS independently affected OS/PFS in WT NSCLC BM, which was consistent with the known literature.
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http://dx.doi.org/10.1093/neuonc/noz155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442419PMC
February 2020

Malignant Transformation of Molecularly Classified Adult Low-Grade Glioma.

Int J Radiat Oncol Biol Phys 2019 12 25;105(5):1106-1112. Epub 2019 Aug 25.

Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio; Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio.

Purpose: Malignant transformation (MT) of adult grade 2 glioma (low-grade glioma [LGG]) is associated with adverse survival. We sought to describe the incidence, outcomes, and risk factors for MT of molecularly classified LGG.

Methods And Materials: We reviewed a single-institutional database of adults who received a diagnosis of LGG with data allowing for molecular classification from 1980 to 2018 to evaluate time to MT and its associated risk factors. MT was defined as pathologic confirmation of grade 3-4 glioma and/or imaging characteristics consistent with MT by multidisciplinary consensus.

Results: Among the included 486 adults with molecularly classified LGG, median age was 39 years (range, 18-78), median tumor size was 3.9 cm (range, 0.3-13.0), and 262 (54%) were male. Molecular classification was IDH1p/19q in 169 (35%), IDH1p/19q in 125 (26%), and IDH in 192 (40%) patients. Adjuvant management was observation in 246 (51%) patients, temozolomide alone in 82 (16%), radiation therapy alone in 63 (13%), and radiation therapy concurrent with temozolomide in 81 (17%). Temozolomide monotherapy was more likely to be given to IDH1p/19q patients (P < .001). Median follow-up was 5.3 years. MT occurred in 84 (17%) patients, with a 5-year freedom from MT of 86% (95% confidence interval [CI], 82%-90%). Median overall survival after MT was 2.4 years (95% CI, 1.5-3.3) and was associated with molecular classification (P = .03) and grade at MT (P < .001). Factors associated with MT were male sex (hazard ratio [HR], 2.1; 95% CI, 1.2-3.6; P = .009), tumor size ≥5 cm (HR, 3.5; 95% CI, 2.0-6.2; P < .001), IDH1p/19q (HR, 2.7; 95% CI, 1.3-5.6; P = .009) or IDH classification (HR, 5.5; 95% CI, 2.5-11.8; P < .001), and adjuvant temozolomide monotherapy (HR, 3.8; 95% CI, 1.4-10.3; P = .008).

Conclusions: MT of LGG has a poor prognosis associated with unfavorable molecular groups. Analysis of our large cohort identified adjuvant temozolomide monotherapy as the only modifiable risk factor for MT and provides the first clinical evidence of temozolomide-associated MT among molecularly classified adult LGG. This novel finding supplements our understanding of temozolomide-induced hypermutation and informs precision management of LGG.
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http://dx.doi.org/10.1016/j.ijrobp.2019.08.025DOI Listing
December 2019

The association of health-related quality of life and cognitive function in patients receiving memantine for the prevention of cognitive dysfunction during whole-brain radiotherapy.

Neurooncol Pract 2019 Jul 3;6(4):274-282. Epub 2018 Dec 3.

Emory University, Atlanta, Georgia, USA.

Background: This study evaluated the association between health-related quality of life (HRQOL) and cognition in patients receiving memantine for prevention of cognitive dysfunction during whole-brain radiotherapy (WBRT).

Methods: Adult patients with brain metastases received WBRT and were randomized to receive placebo or memantine, 20 mg per day, within 3 days of initiating radiotherapy, for 24 weeks. The Functional Assessment of Cancer Therapy-Brain module (FACT-Br) and Medical Outcomes Scale-Cognitive Functioning Scale (MOS-C) were completed in coordination with serial standardized tests of cognitive function.

Results: Of the 508 eligible patients, 442 (87%) consented to participate in the HRQOL portion and contributed to baseline analyses. Evaluable patients at 24 weeks (n = 246) included surviving patients completing FACT-Br, MOS-C, and objective cognitive assessments (n = 146, 59%) and patients alive at time of missed assessment (n = 100, 41%). Baseline cognitive function correlated significantly with FACT-Br and MOS-C self-reports. All domains of objective cognitive function showed declines over time. Neither FACT-Br nor MOS-C differed between the treatment arms. Emotional and functional well-being subscales of the FACT improved over time while the remainder of the FACT-Br domains remained stable. MOS-C scores declined over time.

Conclusion: Baseline cognitive function correlated significantly with FACT-Br and MOS-C scores. No by-arm differences in HRQOL were observed despite differences in objective cognitive function. Patient attrition and poor testing compliance remain significant problems in studies of cognitive function of brain metastases patients and further effort is needed to improve compliance with testing and sensitivity of patient-reported measures.
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http://dx.doi.org/10.1093/nop/npy038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660822PMC
July 2019

Fractionated Gamma Knife radiosurgery for skull base meningiomas: a single-institution experience.

Neurosurg Focus 2019 06;46(6):E8

1Department of Neurosurgery, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University.

OBJECTIVEGamma Knife radiosurgery (GKRS) has been successfully used for the treatment of intracranial meningiomas given its steep dose gradients and high-dose conformality. However, treatment of skull base meningiomas (SBMs) may pose significant risk to adjacent radiation-sensitive structures such as the cranial nerves. Fractionated GKRS (fGKRS) may decrease this risk, but until recently it has not been practical with traditional pin-based systems. This study reports the authors' experience in treating SBMs with fGKRS, using a relocatable, noninvasive immobilization system.METHODSThe authors performed a retrospective review of all patients who underwent fGKRS for SBMs between 2013 and 2018 delivered using the Extend relocatable frame system or the Icon system. Patient demographics, pre- and post-GKRS tumor characteristics, perilesional edema, prior treatment details, and clinical symptoms were evaluated. Volumetric analysis of pre-GKRS, post-GKRS, and subsequent follow-up visits was performed.RESULTSTwenty-five patients met inclusion criteria. Nineteen patients were treated with the Icon system, and 6 patients were treated with the Extend system. The mean pre-fGKRS tumor volume was 7.62 cm3 (range 4.57-13.07 cm3). The median margin dose was 25 Gy delivered in 4 (8%) or 5 (92%) fractions. The median follow-up time was 12.4 months (range 4.7-17.4 months). Two patients (9%) experienced new-onset cranial neuropathy at the first follow-up. The mean postoperative tumor volume reduction was 15.9% with 6 patients (27%) experiencing improvement of cranial neuropathy at the first follow-up. Median first follow-up scans were obtained at 3.4 months (range 2.8-4.3 months). Three patients (12%) developed asymptomatic, mild perilesional edema by the first follow-up, which remained stable subsequently.CONCLUSIONSfGKRS with relocatable, noninvasive immobilization systems is well tolerated in patients with SBMs and demonstrated satisfactory tumor control as well as limited radiation toxicity. Future prospective studies with long-term follow-up and comparison to single-session GKRS or fractionated stereotactic radiotherapy are necessary to validate these findings and determine the efficacy of this approach in the management of SBMs.
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http://dx.doi.org/10.3171/2019.3.FOCUS1963DOI Listing
June 2019

Risk Factors for Progression Among Low-Grade Gliomas After Gross Total Resection and Initial Observation in the Molecular Era.

Int J Radiat Oncol Biol Phys 2019 08 22;104(5):1099-1105. Epub 2019 Apr 22.

Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio; Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio; Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, Ohio. Electronic address:

Purpose: To identify risk factors for progression-free survival (PFS) in the molecular era among patients with low-grade glioma (LGG) who undergo gross total resection (GTR) followed by initial observation.

Methods And Materials: We reviewed patients with World Health Organization grade 2 LGG treated at a single institution. We included only those who underwent magnetic resonance imaging (MRI)-confirmed GTR followed by initial observation. Molecular classification was obtained at either the time of diagnosis or pathology review. Cox proportional hazards regression, the Kaplan-Meier method, and the log-rank test were used. P values <.05 were considered statistically significant.

Results: We included 144 patients who underwent MRI-confirmed GTR between 1994 and 2014 followed by initial observation. Median age was 29 years (interquartile range [IQR], 18-41), median tumor size was 2.7 cm (IQR, 1.8-4.0), and median follow-up was 81 months (IQR, 36-132). Molecular classification was 13% IDH-mutant 1p19q-codeleted; 21% IDH-mutant 1p19q-intact; 39% IDH1-R132H-wildtype; and 28% undetermined. For the entire cohort, 5- and 10-year PFS and overall survival were 71% and 53%, and 98% and 90%, respectively. On multivariate analysis, factors associated with worse PFS included increasing age at diagnosis (hazard ratio [HR], 1.05; 95% CI, 1.00-1.09; P = .03), increasing preoperative tumor size (HR, 1.07; 95% CI, 1.04-1.10; P < .0001), and IDH-mutant 1p19q-intact classification (HR, 3.18; 95% CI, 1.15-8.74, P = .025). Median PFS for patients with IDH-mutant 1p19q-codeleted, IDH-mutant 1p19q-intact, and IDH1-R132H-wildtype tumors were 113 months, 56 months, and not reached, respectively. Molecular classification was significantly associated with PFS (P < .0001) but not overall survival (P = .20).

Conclusions: Among patients with LGG who undergo MRI-confirmed GTR and initial observation in the molecular era, increasing age, increasing tumor size, and IDH-mutant 1p19q-intact classification are associated with worse PFS. Because tumor progression is associated with adverse health-related quality of life, these factors may aid clinicians and patients in the shared decision-making process regarding goals of surgery and timing of postoperative therapy. Further study is required to elucidate why IDH-mutant 1p19q-intact LGGs are at higher risk for early progression.
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http://dx.doi.org/10.1016/j.ijrobp.2019.04.010DOI Listing
August 2019

Clinical Factors Associated With Cost in Head and Neck Cancer: Implications for a Bundled Payment Model.

J Oncol Pract 2019 06 22;15(6):e560-e567. Epub 2019 Apr 22.

3 Levine Cancer Institute, Atrium Health, Charlotte, NC.

Purpose: To determine which factors influence cost in head and neck cancer (HNC) to inform the development of a bundled payment model (BPM).

Methods: Patients with stages 0 to IVB (by American Joint Commission on Cancer, 7th edition) HNC of various sites and histology treated definitively at a single tertiary care center during 2013 were included. Clinical variables and direct cost data were obtained, and their associations were investigated using χ, , Wilcoxon rank sum, and analysis of variance testing. Results were used to develop a BPM.

Results: One hundred fifty patients were included; 87% were white, 74% were men, 48% had oropharyngeal cancer, and 58% had stage IVA disease. Treatment consisted of surgery alone (17%), radiation alone (11%), surgery plus radiation (14%), chemoradiation (45%), and surgery plus chemoradiation (13%). On multivariable analysis, both increasing group stage and number of treatment modalities used were significantly associated with higher cost. Given that stage often dictates treatment, we developed three cost tiers that were based on overall treatment modality. Tier A, the least costly, consisted of single-modality therapy with either surgery alone or radiation alone (median cost divided by the median overall cost of treatment, 0.54; 25th to 75th percentile range, 0.29 to 1.02), followed by tier B, which consisted of bimodality therapy with either chemoradiation or surgery plus radiation (1.03; range, 0.81 to 1.35), followed by tier C, which consisted of trimodality therapy with surgery plus chemoradiation (1.43; range, 1.10 to 1.96).

Conclusion: The number of treatment modalities required is the primary driver of cost in HNC. These data can simplify development of a comprehensive HNC BPM.
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http://dx.doi.org/10.1200/JOP.18.00665DOI Listing
June 2019

Updates in the management of intradural spinal cord tumors: a radiation oncology focus.

Neuro Oncol 2019 06;21(6):707-718

Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.

Primary spinal cord tumors represent a hetereogeneous group of central nervous system malignancies whose management is complex given the relatively uncommon nature of the disease and variety of tumor subtypes, functional neurologic deficits from the tumor, and potential morbidities associated with definitive treatment. Advances in neuroimaging; integration of diagnostic, prognostic, and predictive molecular testing into tumor classification; and developments in neurosurgical techniques have refined the current role of radiotherapy in the multimodal management of patients with primary spinal cord tumors, and corroborated the need for prospective, multidisciplinary discussion and treatment decision making. Radiotherapeutic technological advances have dramatically improved the entire continuum from treatment planning to treatment delivery, and the development of stereotactic radiosurgery and proton radiotherapy provides new radiotherapy options for patients treated in the definitive, adjuvant, or salvage setting. The objective of this comprehensive review is to provide a contemporary overview of the management of primary intradural spinal cord tumors, with a focus on radiotherapy.
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http://dx.doi.org/10.1093/neuonc/noz014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556849PMC
June 2019

The impact of sequencing PD-1/PD-L1 inhibitors and stereotactic radiosurgery for patients with brain metastasis.

Neuro Oncol 2019 08;21(8):1060-1068

Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Taussig Cancer Institute, Cleveland, Ohio.

Background: The response of brain metastases (BM) treated with stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICIs; programmed cell death 1 and its ligand) is of significant interest.

Methods: Patients were divided into cohorts based on ICI sequencing around SRS. The primary outcome was best objective response (BOR) that was lesion specific. Secondary outcomes included overall objective response (OOR), response durability, radiation necrosis (RN), and overall survival (OS).

Results: One hundred fifty patients underwent SRS to 1003 BM and received ICI. Five hundred sixty-four lesions (56%) treated with concurrent ICI (±5 half-lives) demonstrated superior BOR, OOR, and response durability compared with lesions treated with SRS and delayed ICI. Responses were best in those treated with immediate (±1 half-life) ICI (BOR: -100 vs -57%, P < 0.001; complete response: 50 vs 32%; 12-month durable response: 94 vs 71%, P < 0.001). Lesions pre-exposed to ICI and treated with SRS had poorer BOR (-45%) compared with ICI naive lesions (-63%, P < 0.001); best response was observed in ICI naive lesions receiving SRS and immediate ICI (-100%, P < 0.001). The 12-month cumulative incidence of RN with immediate ICI was 3.2% (95% CI: 1.3-5.0%). First radiographic follow-up and best intracranial response were significantly associated with longer OS; steroids were associated with inferior response rates and poorer OS (median 10 vs 25 mo, P = 0.002).

Conclusions: Sequencing of ICI around SRS is associated with overall response, best response, and response durability, with the most substantial effect in ICI naive BM undergoing immediate combined modality therapy. First intracranial response for patients treated with immediate ICI and SRS may be prognostic for OS, whereas steroids are detrimental.
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http://dx.doi.org/10.1093/neuonc/noz046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682202PMC
August 2019

Resection First.

Int J Radiat Oncol Biol Phys 2019 03;103(4):798

Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio.

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http://dx.doi.org/10.1016/j.ijrobp.2018.11.026DOI Listing
March 2019

Stereotactic radiosurgery with concurrent lapatinib is associated with improved local control for HER2-positive breast cancer brain metastases.

J Neurosurg 2019 02;132(2):503-511

Departments of1Radiation Oncology and.

Objective: With increasing survival for patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer in the trastuzumab era, there is an increased risk of brain metastasis. Therefore, there is interest in optimizing intracranial disease control. Lapatinib is a small-molecule dual HER2/epidermal growth factor receptor inhibitor that has demonstrated intracranial activity against HER2+ breast cancer brain metastases. The objective of this study was to investigate the impact of lapatinib combined with stereotactic radiosurgery (SRS) on local control of brain metastases.

Methods: Patients with HER2+ breast cancer brain metastases who underwent SRS from 1997-2015 were included. The primary outcome was the cumulative incidence of local failure following SRS. Secondary outcomes included the cumulative incidence of radiation necrosis and overall survival.

Results: One hundred twenty-six patients with HER2+ breast cancer who underwent SRS to 479 brain metastases (median 5 lesions per patient) were included. Among these, 75 patients had luminal B subtype (hormone receptor-positive, HER2+) and 51 patients had HER2-enriched histology (hormone receptor-negative, HER2+). Forty-seven patients received lapatinib during the course of their disease, of whom 24 received concurrent lapatinib with SRS. The median radiographic follow-up among all patients was 17.1 months. Concurrent lapatinib was associated with reduction in local failure at 12 months (5.7% vs 15.1%, p < 0.01). For lesions in the ≤ 75th percentile by volume, concurrent lapatinib significantly decreased local failure. However, for lesions in the > 75th percentile (> 1.10 cm3), concurrent lapatinib did not significantly improve local failure. Any use of lapatinib after development of brain metastasis improved median survival compared to SRS without lapatinib (27.3 vs 19.5 months, p = 0.03). The 12-month risk of radiation necrosis was consistently lower in the lapatinib cohort compared to the SRS-alone cohort (1.3% vs 6.3%, p < 0.01), despite extended survival.

Conclusions: For patients with HER2+ breast cancer brain metastases, the use of lapatinib concurrently with SRS improved local control of brain metastases, without an increased rate of radiation necrosis. Concurrent lapatinib best augments the efficacy of SRS for lesions ≤ 1.10 cm3 in volume. In patients who underwent SRS for HER2+ breast cancer brain metastases, the use of lapatinib at any time point in the therapy course was associated with a survival benefit. The use of lapatinib combined with radiosurgery warrants further prospective evaluation.
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http://dx.doi.org/10.3171/2018.10.JNS182340DOI Listing
February 2019

Stereotactic radiosurgery with concurrent HER2-directed therapy is associated with improved objective response for breast cancer brain metastasis.

Neuro Oncol 2019 05;21(5):659-668

Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio.

Background: Patients with breast cancer positive for human epidermal growth factor receptor 2 (HER2) remain at high risk of intracranial relapse following treatment and experience increased rates of intracranial failure after stereotactic radiosurgery (SRS). We hypothesized that the addition of concurrent lapatinib to SRS would improve intracranial complete response rates.

Methods: Patients with newly diagnosed HER2-amplified breast cancer brain metastases from 2005-2014 who underwent SRS were included and divided into 2 cohorts based on timing of treatment with lapatinib. Outcome variables included the proportion of patients who achieved an intracranial complete response or progressive disease according to the RECIST 1.1 criteria, as well as individual lesion response rates, distant intracranial failure, and radiation necrosis.

Results: Eighty-four patients with 487 brain metastases met inclusion criteria during the study period. Over 138 treatment sessions, 132 lesions (27%) were treated with SRS and concurrent lapatinib, while 355 (73%) were treated with SRS without lapatinib. Compared with patients treated with SRS alone, patients treated with concurrent lapatinib had higher rates of complete response (35% vs 11%, P = 0.008). On a per-lesion basis, best objective response was superior in the concurrent lapatinib group (median 100% vs 70% reduction, P < 0.001). Concurrent lapatinib was not associated with an increased risk of grade 2+ radiation necrosis (1.0% with concurrent lapatinib vs 3.5% without, P = 0.27). Lapatinib had no protective effect on distant intracranial failure rates (48% vs 49%, P = 0.91).

Conclusion: The addition of concurrent lapatinib to SRS was associated with improved complete response rates among patients with HER2-positive brain metastases.
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http://dx.doi.org/10.1093/neuonc/noz006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6502492PMC
May 2019
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