Publications by authors named "Nadia N Laack"

133 Publications

Imaging Findings of Pediatric Orbital Masses and Tumor Mimics.

Radiographics 2022 May-Jun;42(3):880-897. Epub 2022 Mar 4.

From the Departments of Radiology (A.K.J., J.B.G., L.J.E., G.B.L., J.C.B., W.B., V.M.S.), Ophthalmology (L.A.D.), Neurology (G.F.K.), Neurosurgery (W.B.), and Radiation Oncology (N.N.L.), Mayo Clinic, 200 1st St SW, Rochester, MN 55905.

Pediatric orbital masses are not common but encompass a wide spectrum of benign and malignant entities that range from developmental anomalies to primary and secondary orbital malignancies and metastatic disease. Certain orbital tumors are unique to pediatric patients, such as retinoblastoma and neuroblastoma. Clinical symptoms and signs are often insufficient to differentiate between orbital lesions, and imaging is essential for narrowing the diagnostic considerations and determining the most appropriate management strategy. MRI is the primary imaging modality for evaluating orbital masses in children, with US and CT playing complementary roles. The authors review a spectrum of masses and tumor mimics that affect the pediatric globe and orbit. The shared and differentiating characteristics of pediatric orbital lesions are reviewed. Emphasis is placed on utilizing an orbital compartment-based approach to narrow the differential diagnosis. By using this organizational scheme, the authors describe intraocular processes (retinoblastoma, persistent fetal vasculature, and Coats disease), intraconal lesions (lymphatic malformation, schwannoma, optic nerve sheath meningioma, and optic pathway glioma), extraconal lesions (infantile hemangioma, rhabdomyosarcoma, idiopathic orbital inflammation, lymphoma, venous varix, plexiform neurofibroma, and pleomorphic adenoma of the lacrimal gland), and lesions involving the bony orbit (dermoid cyst, metastatic neuroblastoma, and Langerhans cell histiocytosis). The authors describe the basic management of each entity. Orbital infections and traumatic lesions are beyond the scope of this article. RSNA, 2022.
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http://dx.doi.org/10.1148/rg.210116DOI Listing
May 2022

Development and Internal Validation of a Recursive Partitioning Analysis-Based Model Predictive of Pain Flare Incidence After Spine Stereotactic Body Radiation Therapy.

Pract Radiat Oncol 2022 Feb 10. Epub 2022 Feb 10.

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota. Electronic address:

Purpose: Pain flares are a common acute toxic effect after stereotactic body radiation therapy (SBRT) for spine metastasis. We aimed to identify a subset of patients with the highest rate of pain flare after spine SBRT to optimize prophylactic corticosteroid administration.

Methods And Materials: The data set included 428 patients with 610 treatments. We defined pain flare as acute worsening of pain at the treatment site requiring new or higher dose therapy with corticosteroids, opiates, and/or hospitalization. Data were split into 70% training and 30% validation sets using a random number generator. After feature importance testing and generation of a correlation heatmap, feature extraction was performed via recursive partitioning analysis.

Results: We identified 125 total pain flares (20%). Five variables met significance (P < .02) for model inclusion: renal primary, soft tissue involvement, Bilsky >0, spinal instability neoplastic score >6, and gross tumor volume >8 cc. One point was assigned for each variable. The low-risk group (score = 0, n = 159) had pain flare rates of 7.0% and 13.6% in the training and validation sets; the intermediate-risk group (score = 1, n = 150) had rates of 14.0% and 16.3%; and the high-risk group (score >1, n = 301) had rates of 28.8% and 31.3%. Patients in the high-risk group had higher rates of flare (odds ratio, 3.50; 95% confidence interval, 2.06-5.92) and accumulated health care costs 3 and 6 months post-SBRT, relative to intermediate- and low-risk patients (P < .001).

Conclusions: Our internally validated model identifies a high-risk group of patients more likely to develop a pain flare after spine SBRT, for whom prophylactic steroids may be considered. Evaluation in a clinical trial is warranted.
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http://dx.doi.org/10.1016/j.prro.2022.01.011DOI Listing
February 2022

Development and Assessment of a Predictive Score for Vertebral Compression Fracture After Stereotactic Body Radiation Therapy for Spinal Metastases.

JAMA Oncol 2022 Mar;8(3):412-419

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.

Importance: Vertebral compression fracture (VCF) is a potential adverse effect following treatment with stereotactic body radiation therapy (SBRT) for spinal metastases.

Objective: To develop and assess a risk stratification model for VCF after SBRT.

Design, Setting, And Participants: This retrospective cohort study conducted at a high-volume referral center included 331 patients who had undergone 464 spine SBRT treatments from December 2007 through October 2019. Data analysis was conducted from November 1, 2020, to August 17, 2021. Exclusions included proton therapy, prior surgical intervention, vertebroplasty, or missing data.

Exposures: One and 3 fraction spine SBRT treatments were most commonly delivered. Single-fraction treatments generally involved prescribed doses of 16 to 24 Gy (median, 20 Gy; range, 16-30 Gy) to gross disease compared with multifraction treatment that delivered a median of 30 Gy (range, 21-50 Gy).

Main Outcomes And Measures: The VCF and radiography components of the spinal instability neoplastic score were determined by a radiologist. Recursive partitioning analysis was conducted using separate training (70%), internal validation (15%), and test (15%) sets. The log-rank test was the criterion for node splitting.

Results: Of the 331 participants, 88 were women (27%), and the mean (IQR) age was 63 (59-72) years. With a median follow-up of 21 months (IQR, 11-39 months), we identified 84 VCFs (18%), including 65 (77%) de novo and 19 (23%) progressive fractures. There was a median of 9 months (IQR, 3-21 months) to developing a VCF. From 15 candidate variables, 6 were identified using the backward selection method, feature importance testing, and a correlation heatmap. Four were selected via recursive partitioning analysis: epidural tumor extension, lumbar location, gross tumor volume of more than 10 cc, and a spinal instability neoplastic score of more than 6. One point was assigned to each variable, and the resulting multivariable Cox model had a concordance of 0.760. The hazard ratio per 1-point increase for VCF was 1.93 (95% CI, 1.62-2.30; P < .001). The cumulative incidence of VCF at 2 years (with death as a competing risk) was 6.7% (95% CI, 4.2%-10.7%) for low-risk (score, 0-1; 273 [58.3%]), 17.0% (95% CI, 10.8%-26.7%) for intermediate-risk (score, 2; 99 [21.3%]), and 35.4% (95% CI, 26.7%-46.9%) for high-risk cases (score, 3-4; 92 [19.8%]) (P < .001). Similar results were observed for freedom from VCF using stratification.

Conclusions And Relevance: The results of this cohort study identify a subgroup of patients with high risk for VCF following treatment with SBRT who may potentially benefit from undergoing prophylactic spinal stabilization or vertebroplasty.
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http://dx.doi.org/10.1001/jamaoncol.2021.7008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8796057PMC
March 2022

Comparison of Oncologic Outcomes and Treatment-Related Toxicity of Carbon Ion Radiotherapy and En Bloc Resection for Sacral Chordoma.

JAMA Netw Open 2022 01 4;5(1):e2141927. Epub 2022 Jan 4.

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.

Importance: Maximal resection is the preferred management for sacral chordomas but can be associated with unacceptable morbidity. Outcomes with radiotherapy are poor. Carbon ion radiotherapy (CIRT) is being explored as an alternative when surgery is not preferred.

Objective: To compare oncologic outcomes and treatment-related toxicity of CIRT and en bloc resection for sacral chordoma.

Design, Setting, And Participants: Univariable logistic regression was performed to evaluate the association between treatment type and oncologic and toxicity outcomes in this retrospective cohort study. Nearest-neighbor propensity score matching was used to match the CIRT cohort with the en bloc resection cohort and 10 National Cancer Database (NCDB) cohorts separately, with the objective of obtaining more homogeneous cohorts when comparing treatments. Patient- and tumor-related characteristics from 2 institutional cohorts were collected for patients diagnosed with sacral chordomas between April 1, 1994, and July 31, 2017. The NCDB was queried for data on patients with sacral chordoma from January 1, 2004, to December 31, 2016, as a comparator in overall survival (OS) analyses. Data analysis was conducted from February 24, 2020, to January 16, 2021.

Exposures: En bloc resection, incomplete resection, photon radiotherapy, proton radiotherapy, and CIRT.

Main Outcomes And Measures: Overall survival was estimated using the Kaplan-Meier method and compared using the Cox proportional hazards model. Peripheral motor nerve toxic effects were scored using Common Terminology Criteria for Adverse Events, version 4.03.

Results: A total of 911 patients were included in the study (NCDB: n = 669; median age, 64 [IQR, 52-74] years; 410 [61.3%] men; CIRT: n = 188; median age, 66 [IQR, 58-71] years; 128 [68.1%] men; en bloc surgical resection: n = 54; median age, 53.5 [IQR 49-64] years, 36 [66.7%] men). Comparison of the propensity score-matched institutional en bloc resection and CIRT cohorts revealed no statistically significant difference in OS (CIRT: median OS, 68.1 [95% CI, 44.0-102.6] months; en bloc resection: median OS, 58.6 [95% CI, 25.6-123.5] months; P = .57; hazard ratio, 0.71 [95% CI, 0.25-2.06]; P = .53). The CIRT cohort experienced lower rates of peripheral motor neuropathy (odds ratio, 0.13 [95% CI, 0.04-0.40]; P < .001). On comparison of the propensity score-matched NCDB cohorts with the CIRT cohort, significantly higher OS was found for CIRT compared with margin-positive surgery without adjuvant radiotherapy (CIRT: median OS, 64.7 [95% CI, 57.8-69.7] months; margin-positive surgery without adjuvant radiotherapy: median OS, 60.6 [95% CI, 44.2-69.7] months, P = .03) and primary radiotherapy alone (CIRT: median OS, 64.9 [95% CI 57.0-70.5] months; primary radiotherapy alone: 31.8 [95% CI, 27.9-40.6] months; P < .001).

Conclusions And Relevance: These findings suggest that CIRT can be used as treatment for older patients with high performance status and sacral chordoma in whom surgery is not preferred. CIRT might provide additional benefit for patients who undergo margin-positive resection or who are candidates for primary photon radiotherapy.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.41927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742192PMC
January 2022

Factors Associated With Acute Toxicity in Pediatric Patients Treated With Proton Radiation Therapy: A Report From the Pediatric Proton Consortium Registry.

Pract Radiat Oncol 2022 Mar-Apr;12(2):155-162. Epub 2021 Dec 17.

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota. Electronic address:

Purpose: Limited prospective information regarding acute toxicity in pediatric patients receiving proton therapy (PT) exists. In this study, Pediatric Proton Consortium Registry (PPCR) data was analyzed for factors associated with development of acute toxicity in children receiving passively scattered or pencil beam scanning PT.

Methods And Materials: Pediatric patients treated with PT and enrolled on the PPCR from 2016 to 2017 at 7 institutions were included. Data were entered on presence versus absence of acute general, cardiac, endocrine, eye, gastrointestinal, genitourinary, hematologic, mouth, musculoskeletal, neurologic, psychological, respiratory, and skin toxicities before (baseline) and at the end of PT (acute). Associations between patient and treatment variables with development of acute toxicity were assessed with multivariable modeling.

Results: Of 422 patients included, PT technique was passively scattered in 241 (57%), pencil beam scanning in 180 (43%), and missing in 1 (<1%) patient. Median age was 9.9 years. Daily anesthesia for treatment was used in 169 (40%). Treatments were categorized as craniospinal irradiation (CSI; n = 100, 24%), focal central nervous system PT (n = 157, 38%), or body PT (n = 158, 38%). Passively scattered PT was associated with increased risk of hematologic toxicity compared with pencil beam scanning PT (odds ratio [OR]: 3.03; 95% confidence interval [CI], 1.38-6.70; P = .006). There were no other differences toxicities between PT techniques. Uninsured patients had increased risk of GI (OR: 2.71; 95% CI, 1.12-6.58; P = .027) and hematologic toxicity (OR: 10.67; 95% CI, 2.68-42.46; P <.001). Patients receiving concurrent chemotherapy were more likely to experience skin (OR: 2.45; 95% CI, 1.23-4.88; P = .011), hematologic (OR: 2.87; 95% CI, 1.31-6.25; P = .008), GI (OR: 2.37; 95% CI, 1.33-4.21; P = .003), and mouth toxicities (OR: 2.03; 95% CI, 1.10-3.73; P = .024). Patients receiving 49 to 55 Gy were more likely to experience skin (OR: 2.18; 95% CI, 1.06-4.44; P = .033) toxicity than those receiving <49 Gy.

Conclusions: The PPCR registry highlights broad differences in acute toxicity rates in children receiving PT, and identifies opportunities for improvements in prevention, monitoring, and treatment of toxicities.
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http://dx.doi.org/10.1016/j.prro.2021.10.011DOI Listing
March 2022

Variation in Proton Craniospinal Irradiation Practice Patterns in the United States: A Pediatric Proton Consortium Registry (PPCR) Study.

Int J Radiat Oncol Biol Phys 2022 03 20;112(4):901-912. Epub 2021 Nov 20.

University of California, San Diego, La Jolla, California. Electronic address:

Purpose: Craniospinal irradiation (CSI) is commonly used for pediatric brain tumors with a propensity for spread in craniospinal fluid, principally medulloblastoma. Evolving technology has led to the use of highly conformal radiation therapy (RT) techniques for CSI, including proton therapy. Target delineation and plan coverage are critical for CSI, but there is ongoing controversy and variability in these realms, with little available data on practice patterns. We sought to characterize proton CSI practice patterns in the United States by examining CSI plans in the Pediatric Proton/Photon Consortium Registry (PPCR).

Materials And Methods: PPCR was queried for data on proton CSI patients from 2015 to early 2020. Each plan was manually reviewed, determining patient position; prescription dose; and coverage of optic nerves, vertebral bodies, spinal nerve roots, sacral nerves, and cranial foramina, among other variables. Two radiation oncologists blinded to clinical data and treating institution assessed coverage at the 95% prescription isodose line and per published European Society for Paediatric Oncology guidelines. Variability in coverage was assessed with nonparametric tests and univariate and multivariate logistic regression.

Results: PPCR supplied data for 450 patients, 384 of whom had an evaluable portion of a CSI plan. Most patients (90.3%) were supine. Optic nerves were fully covered in 48.2%; sacral nerves in 87.7%; cranial foramina in 69.3%; and spinal nerves in 95.6%. Vertebral body (VB) sparing was used in 18.6% of skeletally immature cases, increasing over time (P < .001). Coverage in all categories was significantly different among treating institutions, on univariate and multivariate analyses. Cribriform plate deficits were rare, with marginal misses of the foramen ovale (17.4%) and frontal lobe (12%) most common.

Conclusion: We found consistent variation based on treating institution in proton CSI practices including optic nerve, VB, sacral nerve, cranial, and spinal nerve coverage. These data may serve as a baseline quantification of current proton CSI practices in the United States as they continue to evolve.
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http://dx.doi.org/10.1016/j.ijrobp.2021.11.016DOI Listing
March 2022

The role of single-fraction stereotactic radiosurgery for atypical meningiomas (WHO grade II): treatment results based on a 25-year experience.

J Neurooncol 2021 Dec 27;155(3):335-342. Epub 2021 Oct 27.

Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA.

Purpose: To clarify the role of stereotactic radiosurgery (SRS) for atypical meningiomas (AM).

Methods: A retrospective analysis of 68 patients with AM having SRS from 1995 until 2019.

Results: Nineteen patients (28%) had undergone prior external beam radiation therapy (EBRT) (median dose, 54 Gy). The median follow-up period was 52 months. Eighteen (26%), 17 (25%), and 33 (49%) patients received SRS as an upfront adjuvant (≤ 6 months), early salvage (7-18 months), or late salvage treatment (> 18 months), respectively. The 3-, 5-, and 10-year progression-free survivals (PFSs) were 52%, 35%, and 25%, respectively. The 3-, 5-, and 10-year disease-specific survivals were 85%, 78%, and 61%, respectively. Adverse radiation events (AREs) were observed in 12 patients (18%), with increased or new seizures being the most frequent complication (n = 7). Prior EBRT was associated with reduced PFS (HR 5.92, P < 0.01), reduced DSS (HR 5.84, P < 0.01), and an increased risk of ARE (HR 3.31, P = 0.04). Timing of SRS was correlated with reduced PFS for patients having early salvage treatment compared to upfront adjuvant (HR 3.17, P = 0.01) or late salvage treatment (HR 4.39, P < 0.01).

Conclusion: PFS for patients with residual/recurrent AM remains poor despite SRS. Prior EBRT was associated with worse tumor control, higher tumor-related mortality, and an increased risk of ARE. Further study on the timing of SRS is needed to determine if upfront adjunctive SRS improves tumor control compared to salvage SRS.
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http://dx.doi.org/10.1007/s11060-021-03882-9DOI Listing
December 2021

Phase III Trial Adding Vincristine-Topotecan-Cyclophosphamide to the Initial Treatment of Patients With Nonmetastatic Ewing Sarcoma: A Children's Oncology Group Report.

J Clin Oncol 2021 12 15;39(36):4029-4038. Epub 2021 Oct 15.

Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA.

Purpose: The primary aim of this phase III randomized trial was to test whether the addition of vincristine, topotecan, and cyclophosphamide (VTC) to interval compressed chemotherapy improved survival outcomes for patients with previously untreated nonmetastatic Ewing sarcoma.

Methods: Patients were randomly assigned to receive standard five-drug interval compressed chemotherapy (regimen A) for 17 cycles or experimental therapy with five cycles of VTC within the 17 cycles (regimen B). Patients were stratified by age at diagnosis (< 18 years and ≥18 years) and tumor site (pelvic bone, nonpelvic bone, and extraosseous). Tumor volume at diagnosis was categorized as < 200 mL or ≥ 200 mL. Local control occurred following six cycles. Histologic response was categorized as no viable or any viable tumor. Event-free survival (EFS) and overall survival (OS) were compared between randomized groups with stratified log-rank tests.

Results: Of 642 enrolled patients, 309 eligible patients received standard and 320 received experimental therapy. The 5-year EFS and OS were 78% and 87%, respectively. There was no difference in survival outcomes between randomized groups (5-year EFS regimen A regimen B, 78% 79%; = .192; 5-year OS 86% 88%; = .159). Age and primary site did not affect the risk of an EFS event. However, age ≥ 18 years was associated with an increased risk of death at 5 years (hazard ratio 1.84; 95% CI, 1.15 to 2.96; = .009). The 5-year EFS rates for patients with pelvic, nonpelvic bone, and extraosseous primary tumors were 75%, 78%, and 85%, respectively. Tumor volume ≥ 200 mL was significantly associated with lower EFS.

Conclusion: While VTC added to five-drug interval compressed chemotherapy did not improve survival, these outcomes represent the best survival estimates to date for patients with previously untreated nonmetastatic Ewing sarcoma.
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http://dx.doi.org/10.1200/JCO.21.00358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677904PMC
December 2021

Long-Term Report of a Comprehensive Molecular and Genomic Analysis in NRG Oncology/RTOG 0424: A Phase II Study of Radiation and Temozolomide in High-Risk Grade II Glioma.

JCO Precis Oncol 2021 1;5. Epub 2021 Sep 1.

Ohio State University Comprehensive Cancer Center, Columbus, OH.

Purpose: This study sought to determine the prognostic significance of the WHO-defined glioma molecular subgroups along with additional alterations, including promoter methylation and mutations in , , , , and , in NRG/RTOG 0424 using long-term follow-up data.

Methods: Mutations were determined using an Ion Torrent sequencing panel. 1p/19q co-deletion and promoter methylation were determined by Affymetrix OncoScan and Illumina 450K arrays. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and tested using the log-rank test. Hazard ratios were calculated using the Cox proportional hazard model. Multivariable analyses (MVAs) included patient pretreatment characteristics.

Results: We obtained complete molecular data to categorize 80/129 eligible patients within the WHO subgroups. Of these, 26 (32.5%) were mutant/co-deleted, 28 (35%) were mutant/non-co-deleted, and 26 (32.5%) were wild-type. Upon single-marker MVA, both mutant subgroups were associated with significantly better OS and PFS ( values < .001), compared with the wild-type subgroup. promoter methylation was obtained on 76 patients, where 58 (76%) were methylated and 18 (24%) were unmethylated. Single-marker MVAs demonstrated that promoter methylation was statistically significant for OS ( value < .001) and PFS ( value = .003). In a multimarker MVA, one WHO subgroup comparison (mutant/co-deleted wild-type) was significant for OS ( value = .045), whereas methylation did not retain significance.

Conclusion: This study reports the long-term prognostic effect of the WHO molecular subgroups, promoter methylation, and other mutations in NRG/RTOG 0424. These results demonstrate that the WHO molecular classification and both serve as strong prognostic indicators, but that does not appear to add statistically significant prognostic value to the WHO subgrouping, above and beyond and 1p/19q status.
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http://dx.doi.org/10.1200/PO.21.00112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462570PMC
April 2022

Myxopapillary ependymomas; proximity to the conus and its effect on presentation and outcomes.

Surg Neurol Int 2021 30;12:429. Epub 2021 Aug 30.

Department of Neurologic Surgery Mayo Clinic, Rochester, Minnesota, United States.

Background: Myxopapillary ependymomas (MPE) are intradural spinal tumors with a predilection to the filum terminale. Damage to conus medullaris during surgery can result in sphincteric and sexual dysfunction. The purpose of this study is to determine how myxopapillary ependymoma proximity to the conus impacts patient presentation, extent of resection, and clinical outcomes.

Methods: Fifty-one patients who underwent surgical resection of pathologically confirmed myxopapillary ependymoma with at least 1 year of follow-up were included in the study. We collected initial presenting symptoms, distance of the tumor from the conus, extent of resection, and postoperative clinical outcomes including bladder dysfunction.

Results: Average age was 38 years (range 7-75 years) with a male to female ratio of 1.43:1. Patients most commonly presented with pain symptoms (88%), and 12 patients (23.5%) had urologic symptoms on presentation. The mean tumor distance from the tip of the conus was 1.60 cm (10 cm above to 21 cm below the tip of the conus). Patients with tumors in contact with the conus had a significantly higher rate of preoperative urinary symptoms and were more likely (32% vs. 14%) to suffer postoperative urinary sphincteric disturbances. Tumors with direct invasion of the conus medullaris were more likely to require intralesional resection and fail to achieve a gross total resection (GTR).

Conclusion: Patients with MPE in close proximity to the conus were more likely to suffer from long-term morbidity related to urologic issues following surgical resection. Adjuvant radiotherapy may be a viable option for patients who fail to achieve GTR.
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http://dx.doi.org/10.25259/SNI_590_2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422471PMC
August 2021

Ultra-low-dose (boom-boom) radiotherapy for management of recurrent ocular post-transplant lymphoproliferative disorder.

Am J Ophthalmol Case Rep 2021 Sep 15;23:101118. Epub 2021 May 15.

Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA.

Purpose: To report a case of recurrent iris post-transplant lymphoproliferative disorder (PTLD) treated with ultra-low-dose (boom-boom) radiotherapy (RT).

Observations: A 12-year-old Caucasian male with a history of bilateral, recurrent iris PTLD of the extranodal marginal zone lymphoma (MALT) type presented with persistent bilateral anterior chamber cellular infiltration, which was incompletely controlled on topical corticosteroids, and with elevated intraocular pressure (IOP) in the right eye secondary to steroid response. The patient was diagnosed with PTLD recurrence and was successfully treated with ultra-low-dose RT to both eyes in 2 fractions of 2 Gy. At 15 month follow-up the patient maintained complete disease control with normal IOP off all topical ophthalmic medications.

Conclusions And Importance: Ultra-low-dose RT for ocular PTLD of the MALT subtype represents a novel therapeutic approach that may provide a durable treatment response and could be considered as either primary or adjuvant therapy for this rare condition.
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http://dx.doi.org/10.1016/j.ajoc.2021.101118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144319PMC
September 2021

Hippocampal Avoidance Prophylactic Cranial Irradiation for SCLC.

J Thorac Oncol 2021 06;16(6):e41-e42

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota. Electronic address:

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http://dx.doi.org/10.1016/j.jtho.2021.02.019DOI Listing
June 2021

The Role of Biological Effective Dose in Predicting Obliteration After Stereotactic Radiosurgery of Cerebral Arteriovenous Malformations.

Mayo Clin Proc 2021 05;96(5):1157-1164

Department of Neurological Surgery, Mayo Clinic, Rochester, MN; Department of Radiation Oncology, Mayo Clinic, Rochester, MN. Electronic address:

Objective: To determine whether biological effective dose (BED) was predictive of obliteration after stereotactic radiosurgery (SRS) for cerebral arteriovenous malformations (AVMs).

Patients And Methods: We studied patients undergoing single-session AVM SRS between January 1, 1990, and December 31, 2014, with at least 2 years of imaging follow-up. Excluded were patients with syndromic AVM, previous SRS or embolization, and patients treated with volume-staged SRS. Biological effective dose was calculated using a mono-exponential model described by Jones and Hopewell. The primary outcome was likelihood of total obliteration defined by digital subtraction angiography or magnetic resonance imaging (MRI). Variables were analyzed as continuous and dichotomous variables based on the maximum value of (sensitivity-[1-specificity]).

Results: This study included 352 patients (360 AVM, median follow-up, 5.9 years). The median margin dose prescribed was 18.75 Gy (interquartile range [IQR]: 18 to 20 Gy). Two hundred fifty-nine patients (71.9%) had obliteration shown by angiography (n=176) or MRI (n=83) at a median of 36 months after SRS (IQR: 26 to 44 months). Higher BED was associated with increased likelihood of obliteration in univariate Cox regression analyses, when treated as either a dichotomous (≥133 Gy; hazard ratio [HR],1.52; 95% confidence interval [CI], 1.19 to 1.95; P<.001) or continuous variable (HR, 1.00, 95% CI, 1.0002 to 1.005; P=.04). In multivariable analyses including dichotomized BED and location, BED remained associated with obliteration (P=.001).

Conclusion: Biological effective dose ≥133 Gy was predictive of AVM obliteration after single-session SRS within the prescribed margin dose range 15 to 25 Gy. Further study is warranted to determine whether BED optimization should be considered as well as treatment dose for AVM SRS planning.
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http://dx.doi.org/10.1016/j.mayocp.2020.09.041DOI Listing
May 2021

Does the dural resection bed need to be irradiated? Patterns of recurrence and implications for postoperative radiotherapy for temporal lobe gliomas.

Neurooncol Pract 2021 Apr 4;8(2):190-198. Epub 2020 Nov 4.

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, US.

Background: Patterns of recurrence and survival with different surgical and radiotherapy (RT) techniques were evaluated to guide RT target volumes for patients with temporal lobe glioma.

Methods And Materials: This retrospective cohort study included patients with World Health Organization grades II to IV temporal lobe glioma treated with either partial (PTL) or complete temporal lobectomy (CTL) followed by RT covering both the parenchymal and dural resection bed (whole-cavity radiotherapy [WCRT]) or the parenchymal resection bed only (partial-cavity radiotherapy [PCRT]). Patterns of recurrence, progression-free survival (PFS) and overall survival (OS) were evaluated.

Results: Fifty-one patients were included and 84.3% of patients had high-grade glioma (HGG). CTL and PTL were performed for 11 (21.6%) and 40 (78.4%) patients, respectively. Median RT dose was 60 Gy (range, 40-76 Gy). There were 82.4% and 17.6% of patients who received WCRT and PCRT, respectively. Median follow-up time was 18.4 months (range, 4-161 months). Forty-six patients (90.2%) experienced disease recurrence, most commonly at the parenchymal resection bed (76.5%). No patients experienced an isolated dural recurrence. The median PFS and OS for the PCRT and WCRT cohorts were 8.6 vs 10.8 months ( = .979) and 19.9 vs 18.6 months ( = .859), respectively. PCRT was associated with a lower RT dose to the brainstem, optic, and ocular structures, hippocampus, and pituitary.

Conclusion: We identified no isolated dural recurrence and similar PFS and OS regardless of postoperative RT volume, whereas PCRT was associated with dose reduction to critical structures. Omission of dural RT may be considered a reasonable alternative approach. Further validation with larger comparative studies is warranted.
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http://dx.doi.org/10.1093/nop/npaa073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049436PMC
April 2021

Salvage Radiosurgery for Recurrent Supratentorial Primitive Neuroectodermal Tumors: A Single Institutional Series and Review of the Literature.

Stereotact Funct Neurosurg 2021 21;99(5):405-411. Epub 2021 Apr 21.

Department of Neurological Surgery, Mayo Clinic, Rochester, Minnesota, USA.

Introduction: Supratentorial primitive neuroectodermal tumor is a rare, aggressive intrinsic brain tumor with limited treatment options for recurrent disease. SRS as a treatment modality in the recurrent setting was investigated.

Methods: A retrospective review of 8 patients treated with SRS for local or distant recurrence of supratentorial PNET from 1999 to 2014 was conducted.

Results: Thirty-six tumors were treated in 15 sessions in 8 patients. The median patient age was 22.5 (interquartile range [IQR], 14.75-43.5 years) with a median 21-month period from diagnosis until SRS (IQR, 16-23.75 months). The median prescription isodose volume was 1.85 cm3 (IQR, 1.85-7.02 cm3); median tumor margin dose was 18 Gy (IQR 14-20 Gy); and median isocenters was 2 (range 1-13). No patients experienced adverse radiation effects. All but 1 patient died, and the median overall survival was 32 months (IQR, 26.75-53.5 months) with median overall survival following SRS of 9.5 months (IQR, 5.25-30 months). Univariate analysis failed to demonstrate a statistically significant association between age, number of gamma knife treatments, interval to gamma knife, and margin radiation dose with overall survival.

Discussion/conclusion: This series supports the use of SRS in patients with recurrent supratentorial PNET following multimodal therapy.
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http://dx.doi.org/10.1159/000515544DOI Listing
October 2021

Outcome comparison of patients who develop leptomeningeal disease or distant brain recurrence after brain metastases resection cavity radiosurgery.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab036. Epub 2021 Mar 2.

Department of Neurologic Surgery, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA.

Background: To compare the outcomes between patients with leptomeningeal disease (LMD) and distant brain recurrence (DBR) after stereotactic radiosurgery (SRS) brain metastases (BM) resection cavity.

Methods: Twenty-nine patients having single-fraction SRS after BM resection who developed either LMD ( = 11) or DBR ( = 18) as their initial and only site of intracranial progression were retrospectively reviewed.

Results: Patients developing LMD more commonly had a metachronous presentation (91% vs 50%, = .04) and recursive partitioning class 1 status (45% vs 6%, = .02). There was no difference in the median time from SRS to the development of LMD or DBR (5.0 vs 3.8 months, = .68). The majority of patients with LMD (10/11, 91%) developed the nodular variant (nLMD). Treatment for LMD was repeat SRS ( = 4), whole-brain radiation therapy (WBRT; = 5), resection + WBRT ( = 1), and no treatment ( = 1). Treatment for DBR was repeat SRS ( = 9), WBRT ( = 3), resection + resection cavity SRS ( = 1), and no treatment ( = 5). Median overall survival (OS) from time of resection cavity SRS was 15.7 months in the LMD group and 12.7 months in the DBR group ( = .60), respectively. Median OS in salvage SRS and salvage WBRT were 25.4 and 5.0 months in the nLMD group ( = .004) while 18.7 and 16.2 months in the DBR group ( = .30), respectively.

Conclusions: Following BM resection cavity SRS, nLMD recurrence is much more frequent than classical LMD. Salvage SRS may be considered for selected patients with nLMD, reserving salvage WBRT for patients with extensive intracranial disease without compromising survival. Further study with larger numbers of patients is needed.
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http://dx.doi.org/10.1093/noajnl/vdab036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034660PMC
March 2021

Memantine for Mitigation of Neurocognitive Toxicity Following Radiation to the Brain.

JCO Glob Oncol 2021 01;7:27-28

Danielle A. Cunningham, MD; Paul D. Brown, MD; and Nadia N. I. Laack, MD, Department of Radiation Oncology, Mayo Clinic, Rochester, MN.

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http://dx.doi.org/10.1200/GO.20.00551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081539PMC
January 2021

Long-Term Control after Radiosurgery for a Recurrent Supratentorial Primitive Neuroectodermal Tumor: A Case Report and Review of the Literature.

Stereotact Funct Neurosurg 2021 16;99(3):267-269. Epub 2020 Dec 16.

Department of Neurological Surgery, Mayo Clinic, Rochester, Minnesota, USA.

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http://dx.doi.org/10.1159/000512093DOI Listing
October 2021

A multi-institutional phase 2 trial of stereotactic body radiotherapy in the treatment of bone metastases in pediatric and young adult patients with sarcoma.

Cancer 2021 03 10;127(5):739-747. Epub 2020 Nov 10.

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Background: Metastasectomy is standard of care for pediatric patients with metastatic sarcoma with limited disease. For patients with unresectable disease, stereotactic body radiotherapy (SBRT) may serve as an alternative. Herein, the authors report the results of a prospective, multi-institutional phase 2 trial of SBRT in children and young adults with metastatic sarcoma.

Methods: Patients aged >3 years and ≤40 years with unresected, osseous metastatic nonrhabdomyosarcoma sarcomas of soft tissue and bone were eligible. Patients received SBRT to a dose of 40 Gray (Gy) in 5 fractions. Local control (LC), progression-free survival (PFS), and overall survival (OS) were calculated using the Kaplan-Meier method.

Results: Fourteen patients with a median age of 17 years (range, 4-25 years) were treated to 37 distinct metastatic lesions. With a median follow-up of 6.8 months (30.5 months in surviving patients), the Kaplan-Meier patient-specific and lesion-specific LC rates at 6 months were 89% and 95%, respectively. The median PFS was 6 months and the median OS was 24 months. In a post hoc analysis, PFS (median, 9.3 months vs 3.7 months; log-rank P = .03) and OS (median not reached vs 12.7 months; log-rank P = .02) were improved when all known sites of metastatic disease were consolidated with SBRT compared with partial consolidation. SBRT was well tolerated, with 2 patients experiencing grade 3 toxicities.

Conclusions: SBRT achieved high rates of LC in pediatric patients with inoperable metastatic nonrhabdomyosarcoma sarcomas of soft tissue and bone. These results suggest that the ability to achieve total consolidation of metastatic disease with SBRT is associated with improved PFS and OS.
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http://dx.doi.org/10.1002/cncr.33306DOI Listing
March 2021

The Importance of Verification CT-QA Scans in Patients Treated with IMPT for Head and Neck Cancers.

Int J Part Ther 2020 3;7(1):41-53. Epub 2020 Aug 3.

Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.

Purpose: To understand how verification computed tomography-quality assurance (CT-QA) scans influenced clinical decision-making to replan patients with head and neck cancer and identify predictors for replanning to guide intensity-modulated proton therapy (IMPT) clinical practice.

Patients And Methods: We performed a quality-improvement study by prospectively collecting data on 160 consecutive patients with head and neck cancer treated using spot-scanning IMPT who underwent weekly verification CT-QA scans. Kaplan-Meier estimates were used to determine the cumulative probability of a replan by week. Predictors for replanning were determined with univariate (UVA) and multivariate (MVA) Cox model hazard ratios (HRs). Logistic regression was used to determine odds ratios (ORs).  < .05 was considered statistically significant.

Results: Of the 160 patients, 79 (49.4%) had verification CT-QA scans, which prompted a replan. The cumulative probability of a replan by week 1 was 13.7% (95% confidence interval [CI], 8.82-18.9), week 2, 25.0% (95% CI, 18.0-31.4), week 3, 33.1% (95% CI, 25.4-40.0), week 4, 45.6% (95% CI, 37.3-52.8), and week 5 and 6, 49.4% (95% CI, 41.0-56.6). Predictors for replanning were sinonasal disease site (UVA: HR, 1.82,  = .04; MVA: HR, 3.64,  = .03), advanced stage disease (UVA: HR, 4.68,  < .01; MVA: HR, 3.10,  < .05), dose > 60 Gy equivalent (GyE; relative biologic effectiveness, 1.1) (UVA: HR, 1.99,  < .01; MVA: HR, 2.20,  < .01), primary disease (UVA: HR, 2.00 versus recurrent,  = .01; MVA: HR, 2.46,  = .01), concurrent chemotherapy (UVA: HR, 2.05,  < .01; MVA: not statistically significant [NS]), definitive intent treatment (UVA: HR, 1.70 versus adjuvant,  < .02; MVA: NS), bilateral neck treatment (UVA: HR, 2.07,  = .03; MVA: NS), and greater number of beams (5 beam UVA: HR, 5.55 versus 1 or 2 beams,  < .02; MVA: NS). Maximal weight change from baseline was associated with higher odds of a replan (≥3 kg: OR, 1.97,  = .04; ≥ 5 kg: OR, 2.13,  = .02).

Conclusions: Weekly verification CT-QA scans frequently influenced clinical decision-making to replan. Additional studies that evaluate the practice of monitoring IMPT-treated patients with weekly CT-QA scans and whether that improves clinical outcomes are warranted.
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http://dx.doi.org/10.14338/IJPT-20-00006.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574830PMC
August 2020

Reducing Heart Dose with Protons and Cardiac Substructure Sparing for Mediastinal Lymphoma Treatment.

Int J Part Ther 2020 4;7(1):1-12. Epub 2020 Sep 4.

Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.

Purpose: Electrocardiogram-gated computed tomography with coronary angiography can be used for cardiac substructure sparing (CSS) optimization, which identifies and improves avoidance of cardiac substructures when treating with intensity modulated radiotherapy (IMRT). We investigated whether intensity modulated proton therapy (IMPT) would further reduce dose to cardiac substructures for patients with mediastinal lymphoma.

Patients And Methods: Twenty-one patients with mediastinal lymphoma were enrolled and underwent electrocardiogram-gated computed tomography angiography during or shortly after simulation for radiotherapy planning. Thirteen patients with delineated cardiac substructures underwent comparative planning with both IMPT and IMRT. Plans were normalized for equivalent (95%) target volume coverage for treatment comparison.

Results: Thirteen patients met criteria for this study. The median size of the mediastinal lymphadenopathy was 7.9 cm at the greatest diameter. Compared with IMRT-CSS, IMPT-CSS significantly reduced mean dose to all cardiac substructures, including 3 coronary arteries and 4 cardiac valves. Use of IMPT significantly reduced average whole-heart dose from 9.6 to 4.9 Gy ( < .0001), and average mean lung dose was 9.7 vs 5.8 Gy ( < .0001). Prospectively defined clinically meaningful improvement was observed in at least 1 coronary artery in 9 patients (69%), at least 1 cardiac valve in 10 patients (77%), and whole heart in all 13 patients.

Conclusions: For patients with mediastinal lymphoma, IMPT-CSS treatment planning significantly reduced radiation dose to cardiac substructures. The significant improvements outlined in this study for proton therapy suggest possible clinical improvement in alignment with previous analyses of CSS optimization.
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http://dx.doi.org/10.14338/IJPT-20-00010.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574827PMC
September 2020

Practice patterns and recommendations for pediatric image-guided radiotherapy: A Children's Oncology Group report.

Pediatr Blood Cancer 2020 10 9;67(10):e28629. Epub 2020 Aug 9.

Department of Radiation Oncology, Northwestern University, Chicago, Illinois.

This report by the Radiation Oncology Discipline of Children's Oncology Group (COG) describes the practice patterns of pediatric image-guided radiotherapy (IGRT) based on a member survey and provides practice recommendations accordingly. The survey comprised of 11 vignettes asking clinicians about their recommended treatment modalities, IGRT preferences, and frequency of in-room verification. Technical questions asked physicists about imaging protocols, dose reduction, setup correction, and adaptive therapy. In this report, the COG Radiation Oncology Discipline provides an IGRT modality/frequency decision tree and the expert guidelines for the practice of ionizing image guidance in pediatric radiotherapy patients.
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http://dx.doi.org/10.1002/pbc.28629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774502PMC
October 2020

Comprehensive Genomic Analysis in NRG Oncology/RTOG 9802: A Phase III Trial of Radiation Versus Radiation Plus Procarbazine, Lomustine (CCNU), and Vincristine in High-Risk Low-Grade Glioma.

J Clin Oncol 2020 10 24;38(29):3407-3417. Epub 2020 Jul 24.

The Ohio State University, Columbus, OH.

Purpose: NRG Oncology/RTOG 9802 (ClinicalTrials.gov Identifier: NCT00003375) is a practice-changing study for patients with WHO low-grade glioma (LGG, grade II), as it was the first to demonstrate a survival benefit of adjuvant chemoradiotherapy over radiotherapy. This post hoc study sought to determine the prognostic and predictive impact of the WHO-defined molecular subgroups and corresponding molecular alterations within NRG Oncology/RTOG 9802.

Methods: mutations were determined by immunohistochemistry and/or deep sequencing. A custom Ion AmpliSeq panel was used for mutation analysis. 1p/19q codeletion and promoter methylation were determined by copy-number arrays and/or Illumina 450K array, respectively. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Hazard ratios (HRs) were calculated using the Cox proportional hazard model and tested using the log-rank test. Multivariable analyses (MVAs) were performed incorporating treatment and common prognostic factors as covariates.

Results: Of the eligible patients successfully profiled for the WHO-defined molecular groups (n = 106/251), 26 (24%) were wild type, 43 (41%) were mutant/non-codeleted, and 37(35%) were mutant/codeleted. MVAs demonstrated that WHO subgroup was a significant predictor of PFS after adjustment for clinical variables and treatment. Notably, treatment with postradiation chemotherapy (PCV; procarbazine, lomustine (CCNU), and vincristine) was associated with longer PFS (HR, 0.32; = .003; HR, 0.13; < .001) and OS (HR, 0.38; = .013; HR, 0.21; = .029) in the mutant/non-codeleted and mutant/codeleted subgroups, respectively. In contrast, no significant difference in either PFS or OS was observed with the addition of PCV in the wild-type subgroup.

Conclusion: This study is the first to report the predictive value of the WHO-defined diagnostic classification in a set of uniformly treated patients with LGG in a clinical trial. Importantly, this post hoc analysis supports the notion that patients with -mutant high-risk LGG regardless of codeletion status receive benefit from the addition of PCV.
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http://dx.doi.org/10.1200/JCO.19.02983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527157PMC
October 2020

Prediction of MGMT Status for Glioblastoma Patients Using Radiomics Feature Extraction From F-DOPA-PET Imaging.

Int J Radiat Oncol Biol Phys 2020 12 4;108(5):1339-1346. Epub 2020 Jul 4.

Department of Radiation Oncology, Mayo Clinic, Jacksonville, Florida. Electronic address:

Purpose: Methylation of the O-methylguanine methyltransferase (MGMT) gene promoter is associated with improved treatment response and survival in patients with glioblastoma (GB), but the necessary pathologic specimen can be nondiagnostic. In this study, we assessed whether radiomics features from pretreatment F-DOPA positron emission tomography (PET) imaging could be used to predict pathologic MGMT status.

Methods And Materials: This study included 86 patients with newly diagnosed GB, split into 3 groups (training, validating, and predicting). We performed a radiomics analysis on F-DOPA PET images by extracting features from 2 tumor-based contours: a "Gold" contour of all abnormal uptake per expert nuclear medicine physician and a high-grade glioma (HGG) contour based on a tumor-to-normal hemispheric ratio >2.0, representing the most aggressive components. Feature selection was performed by comparing the weighted feature importance and filtering with bivariate analysis. Optimization of model parameters was explored using grid search with selected features. The stability of the model with increasing input features was also investigated for model robustness. The model predictions were then applied by comparing the overall survival probability of the patients with GB and unknown MGMT status versus those with known MGMT status.

Results: A radiomics signature was constructed to predict MGMT methylation status. Using features extracted from HGG contour alone with a random forest model, we achieved 80% ± 10% accuracy for 95% confidence level in predicting MGMT status. The prediction accuracy was not improved with the addition of the Gold contour or with more input features. The model was applied to the patients with unknown MGMT methylation status. The prediction results are consistent with what is expected using overall survival as a surrogate.

Conclusions: This study suggests that 3 features from radiomics modeling of F-DOPA PET imaging can predict MGMT methylation status with reasonable accuracy. These results could provide valuable therapeutic guidance for patients in whom MGMT testing is inconclusive or nondiagnostic.
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http://dx.doi.org/10.1016/j.ijrobp.2020.06.073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680434PMC
December 2020

Brain metastases resection cavity radio-surgery based on T2-weighted MRI: technique assessment.

J Neurooncol 2020 May 17;148(1):89-95. Epub 2020 Apr 17.

Department of Radiation Oncology, Mayo Clinic College of Medicine and Science, 200 First St SW, Rochester, MN, 55905, USA.

Purpose: Stereotactic radiosurgery (SRS) is commonly performed after surgical resection of brain metastases to reduce the chance of local tumor recurrence while maintaining cognitive function. Target delineation in these cases is typically based off T1-weighted post-gadolinium MRI (T1Gd). In this study, we report outcomes for patients having postoperative SRS in which the planning target volume (PTV) was based on T2-weighted MRI (T2W).

Methods: Sixty-two consecutive patients having single-fraction SRS after brain metastases resection were retrospectively reviewed. Excluded were patients with prior whole brain radiation therapy, multiple resection cavities, and small cell pathologies.

Results: The median time from surgery to SRS was 11 days; 26 patients (42%) had SRS ≤ 7 days. The median PTV was 8.0 cm; the median margin dose was 18 Gy. The crude rates of local tumor control (LC), leptomeningeal disease (LMD), distant brain recurrence (DBR), and radiation necrosis (RN) were 85%, 19%, 37%, and 2%, respectively. The 1-year LC, LMD, DBR, and RN rates were 88%, 25%, 36%, and 0%, respectively. No tumor or dosimetric factor was associated with LC. Sub-total tumor resection was a risk factor for LMD (HR 5.11, P = 0.003), whereas patients with multiple brain metastases had a greater risk of DBR (HR 2.88, P = 0.01). The median PTV was smaller compared to the median PTV based off the consensus guidelines utilizing T1Gd MRI (8.0 cm vs. 9.1 cm, P = 0.004).

Conclusion: T2W MRI provided accurate resection cavity delineation even in the early postoperative period and was associated with decreased PTV compared to T1Gd MRI in the majority of cases.
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http://dx.doi.org/10.1007/s11060-020-03492-xDOI Listing
May 2020

Phase 2 Study of a Temozolomide-Based Chemoradiation Therapy Regimen for High-Risk, Low-Grade Gliomas: Long-Term Results of Radiation Therapy Oncology Group 0424.

Int J Radiat Oncol Biol Phys 2020 07 3;107(4):720-725. Epub 2020 Apr 3.

Miami Cancer Institute, Kendall, Florida.

Purpose: To report the long-term outcomes of the RTOG 0424 study of a high-risk, low-grade glioma population treated with concurrent and adjuvant temozolomide (TMZ) and radiation therapy (RT).

Methods And Materials: For this single-arm, phase 2 study, patients with low-grade gliomas with ≥3 risk factors (age ≥40 years, astrocytoma, bihemispheric tumor, size ≥6 cm, or preoperative neurologic function status >1) received RT (54 Gy in 30 fractions) with TMZ and up to 12 cycles of post-RT TMZ. The initial primary endpoint P was overall survival (OS) at 3 years after registration. Secondary endpoints included progression-free survival (PFS) and the association of survival outcomes with methylation status. The initial 3-year report of this study was published in 2015.

Results: The study accrued 136 patients, of whom 129 were analyzable. The median follow-up for surviving patients was 9.0 years. The 3-year OS was 73.5% (95% confidence interval, 65.8%-81.1%), numerically superior to the 3-year OS historical control of 54% (P < .001). The median survival time was 8.2 years (95% confidence interval, 5.6-9.1). Five- and 10-year OS rates were 60.9% and 34.6%, respectively, and 5- and 10-year PFS rates were 46.8% and 25.5%, respectively.

Conclusions: The long-term results confirmed the findings from the initial report for efficacy, suggesting OS and PFS outcomes with the RT-TMZ regimen exceeded historical control groups treated with radiation alone. Toxicity was acceptable.
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http://dx.doi.org/10.1016/j.ijrobp.2020.03.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456814PMC
July 2020

Hippocampal Avoidance During Whole-Brain Radiotherapy Plus Memantine for Patients With Brain Metastases: Phase III Trial NRG Oncology CC001.

J Clin Oncol 2020 04 14;38(10):1019-1029. Epub 2020 Feb 14.

Vanderbilt University Medical Center, Ingram Cancer Center, Nashville, TN.

Purpose: Radiation dose to the neuroregenerative zone of the hippocampus has been found to be associated with cognitive toxicity. Hippocampal avoidance (HA) using intensity-modulated radiotherapy during whole-brain radiotherapy (WBRT) is hypothesized to preserve cognition.

Methods: This phase III trial enrolled adult patients with brain metastases to HA-WBRT plus memantine or WBRT plus memantine. The primary end point was time to cognitive function failure, defined as decline using the reliable change index on at least one of the cognitive tests. Secondary end points included overall survival (OS), intracranial progression-free survival (PFS), toxicity, and patient-reported symptom burden.

Results: Between July 2015 and March 2018, 518 patients were randomly assigned. Median follow-up for alive patients was 7.9 months. Risk of cognitive failure was significantly lower after HA-WBRT plus memantine versus WBRT plus memantine (adjusted hazard ratio, 0.74; 95% CI, 0.58 to 0.95; = .02). This difference was attributable to less deterioration in executive function at 4 months (23.3% 40.4%; = .01) and learning and memory at 6 months (11.5% 24.7% [ = .049] and 16.4% 33.3% [ = .02], respectively). Treatment arms did not differ significantly in OS, intracranial PFS, or toxicity. At 6 months, using all data, patients who received HA-WBRT plus memantine reported less fatigue ( = .04), less difficulty with remembering things ( = .01), and less difficulty with speaking ( = .049) and using imputed data, less interference of neurologic symptoms in daily activities ( = .008) and fewer cognitive symptoms ( = .01).

Conclusion: HA-WBRT plus memantine better preserves cognitive function and patient-reported symptoms, with no difference in intracranial PFS and OS, and should be considered a standard of care for patients with good performance status who plan to receive WBRT for brain metastases with no metastases in the HA region.
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http://dx.doi.org/10.1200/JCO.19.02767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106984PMC
April 2020

Final report from Intergroup NCCTG 86-72-51 (Alliance): a phase III randomized clinical trial of high-dose versus low-dose radiation for adult low-grade glioma.

Neuro Oncol 2020 06;22(6):830-837

Wake Forest Baptist Health, Winston-Salem, North Carolina.

Background: The optimal radiation dose for adult supratentorial low-grade glioma is unknown. The aim of this study was to provide a final update on oncologic and cognitive outcomes of high-dose versus low-dose radiation for low-grade glioma.

Methods: Between 1986 and 1994, 203 patients with supratentorial low-grade glioma were randomized (1:1) to 50.4 Gy in 28 fractions versus 64.8 Gy in 36 fractions after any degree of resection.

Results: For all patients, median overall survival (OS) was 8.4 years (95% CI: 7.2-10.8). Median progression-free survival (PFS) was 5.2 years (95% CI: 4.3-6.6). Median follow-up is 17.2 years for the 33 patients still alive. High-dose radiation did not improve 15-year OS (22.4%) versus low-dose radiation (24.9%, log-rank P = 0.978) or 15-year PFS (high dose, 15.2% vs low dose, 9.5%; P = 0.7142). OS was significantly better for patients with preoperative tumor diameter <5 cm and baseline Mini-Mental State Examination (MMSE) >27 and who underwent gross total resection. PFS was improved for patients with oligodendroglioma versus astrocytoma, preoperative tumor diameter <5 cm, patients who had gross total resection, and patients with baseline MMSE >27. For patients who had normal MMSE at baseline, at 7 years only 1 patient (5%) had a clinically significant decrease in MMSE from the previous time point, with the remainder (95%) stable. None had decrease in MMSE at 10, 12, or 15 years.

Conclusions: Long-term follow-up indicates no benefit to high-dose over low-dose radiation for low-grade gliomas. Cognitive function appeared to be stable after radiation as measured by MMSE.
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http://dx.doi.org/10.1093/neuonc/noaa021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283016PMC
June 2020
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