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Article ; Online: Do Not Forget About the Importance of Loco-Regional Therapy in Melanoma Management.

Wuthrick, Evan J / Chablani, Priyanka

2019 Volume 29, Issue 2, Page(s) 166–170

Abstract: Immunotherapy agents have significantly changed the landscape of melanoma treatment over the past decade. Paradigm shifts in treatment require reanalysis of the treatment algorithms in melanoma. Despite surgical excision, certain high risk patients with ... ...

Abstract	Immunotherapy agents have significantly changed the landscape of melanoma treatment over the past decade. Paradigm shifts in treatment require reanalysis of the treatment algorithms in melanoma. Despite surgical excision, certain high risk patients with desmoplastic melanoma remain at high risk for local recurrence and retrospective data suggests improvement in local control with adjuvant radiation therapy. Likewise, despite surgical excision and effective systemic therapy agents, patients with extracapsular extension and other high risk features are at substantial risk of nodal basin (regional) recurrence. Adjuvant radiation therapy has been demonstrated to reduce the local recurrence risk. Despite these benefits, adjuvant radiation therapy in melanoma remains controversial in part because its use has not been definitively demonstrated to improve overall or disease-free survival in a randomized prospective study.
MeSH term(s)	Combined Modality Therapy ; Disease-Free Survival ; Humans ; Immunotherapy ; Lymph Node Excision ; Lymphatic Metastasis ; Melanoma/pathology ; Melanoma/surgery ; Melanoma/therapy ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Radiotherapy, Adjuvant ; Skin Neoplasms/pathology ; Skin Neoplasms/surgery ; Skin Neoplasms/therapy ; Melanoma, Cutaneous Malignant
Language	English
Publishing date	2019-04-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1146999-7
ISSN	1532-9461 ; 1053-4296
ISSN (online)	1532-9461
ISSN	1053-4296
DOI	10.1016/j.semradonc.2018.11.006
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Article ; Online: A Deep Dive into the Diagnosis and Management of Regional Lymph Node Metastases.

Wuthrick, Evan J / Harrison, Louis B

Seminars in radiation oncology

2019 Volume 29, Issue 2, Page(s) 91–92

MeSH term(s)	Biomarkers, Tumor/analysis ; Diagnostic Imaging ; Humans ; Lymph Node Excision ; Lymphatic Metastasis/diagnosis ; Lymphatic Metastasis/pathology ; Lymphatic Metastasis/prevention & control ; Neoplasm Staging
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2019-03-12
Publishing country	United States
Document type	Editorial ; Introductory Journal Article
ZDB-ID	1146999-7
ISSN	1532-9461 ; 1053-4296
ISSN (online)	1532-9461
ISSN	1053-4296
DOI	10.1016/j.semradonc.2018.11.009
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Article ; Online: Current and future approaches in the surgical management of T3b/T4 primary and locoregionally advanced melanoma.

Sondak, Vernon K / Neves, Rogerio I / Wuthrick, Evan J / Messina, Jane L / Khushalani, Nikhil I

Cancer

2022 Volume 128, Issue 21, Page(s) 3764–3771

Abstract: Currently accepted principles of surgical management-margin width, use of sentinel node biopsy, performance of radical node dissections for node-positive cases-and some aspects of postoperative management (use of radiation for desmoplastic melanoma ... ...

Abstract	Currently accepted principles of surgical management-margin width, use of sentinel node biopsy, performance of radical node dissections for node-positive cases-and some aspects of postoperative management (use of radiation for desmoplastic melanoma primaries and for clinically node-positive disease) will change in the future with the potential widespread adoption of adjuvant and neoadjuvant therapies.
MeSH term(s)	Humans ; Lymph Node Excision ; Margins of Excision ; Melanoma/pathology ; Sentinel Lymph Node Biopsy ; Skin Neoplasms/pathology ; Skin Neoplasms/surgery
Language	English
Publishing date	2022-09-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.34449
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Article ; Online: Clinical outcomes of melanoma brain metastases treated with nivolumab and ipilimumab alone versus nivolumab and ipilimumab with stereotactic radiosurgery.

Tang, Joseph D / Mills, Matthew N / Nakashima, Justyn / Dohm, Ammoren E / Khushalani, Nikhil I / Forsyth, Peter A / Vogelbaum, Michael A / Wuthrick, Evan J / Yu, Hsiang-Hsuan M / Oliver, Daniel E / Liu, James K C / Ahmed, Kamran A

Journal of neuro-oncology

2024 Volume 166, Issue 3, Page(s) 431–440

Abstract: Purpose: Upfront dual checkpoint blockade with immune checkpoint inhibitors (ICI) has demonstrated efficacy for treating melanoma brain metastases (MBM) in asymptomatic patients. Whether the combination of stereotactic radiosurgery (SRS) with dual ... ...

Abstract	Purpose: Upfront dual checkpoint blockade with immune checkpoint inhibitors (ICI) has demonstrated efficacy for treating melanoma brain metastases (MBM) in asymptomatic patients. Whether the combination of stereotactic radiosurgery (SRS) with dual checkpoint blockade improves outcomes over dual-checkpoint blockade alone is unknown. We evaluated clinical outcomes of patients with MBM receiving ICI with nivolumab and ipilimumab, with and without SRS. Methods: 49 patients with 158 MBM receiving nivolumab and ipilimumab for untreated MBM between 2015 and 2022 were identified at our institution. Patient and tumor characteristics including age, Karnofsky Performance Status (KPS), presence of symptoms, cancer history, MBM burden, and therapy course were recorded. Outcomes measured from initiation of MBM-directed therapy included overall survival (OS), local control (LC), and distant intracranial control (DIC). Time-to-event analysis was conducted with the Kaplan-Meier method. Results: 25 patients with 74 MBM received ICI alone, and 24 patients with 84 MBM received concurrent SRS. Median follow-up was 24 months. No differences in age (p = 0.96), KPS (p = 0.85), presence of symptoms (p = 0.79), prior MBM (p = 0.68), prior MBM-directed surgery (p = 0.96) or SRS (p = 0.68), MBM size (p = 0.67), or MBM number (p = 0.94) were seen. There was a higher rate of nivolumab and ipilimumab course completion in the SRS group (54% vs. 24%; p = 0.029). The SRS group received prior immunotherapy more often than the ICI alone group (54% vs. 8.0%; p < 0.001). There was no significant difference in 1-year OS (72% vs. 71%, p = 0.20) and DIC (63% v 51%, p = 0.26) between groups. The SRS group had higher 1-year LC (92% vs. 64%; p = 0.002). On multivariate analysis, LC was improved with combination therapy (AHR 0.38, p = 0.01). Conclusion: In our analysis, patients who received SRS with nivolumab and ipilimumab had superior LC without increased risk of toxicity or compromised immunotherapy treatment completion despite the SRS cohort having higher rates of prior immunotherapy. Further prospective study of combination nivolumab and ipilimumab with SRS is warranted.
MeSH term(s)	Humans ; Ipilimumab/therapeutic use ; Melanoma/pathology ; Nivolumab/therapeutic use ; Radiosurgery/methods ; Prospective Studies ; Antineoplastic Agents, Immunological/therapeutic use ; Brain Neoplasms/drug therapy ; Brain Neoplasms/secondary ; Retrospective Studies
Chemical Substances	Ipilimumab ; Nivolumab (31YO63LBSN) ; Antineoplastic Agents, Immunological
Language	English
Publishing date	2024-02-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	604875-4
ISSN	1573-7373 ; 0167-594X
ISSN (online)	1573-7373
ISSN	0167-594X
DOI	10.1007/s11060-023-04543-9
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Article: Delivery of Online Adaptive MRI-Guided Radiation Therapy for a Deaf Patient.

Linkowski, Lauren C / Sim, Austin J / Redler, Gage / Brohl, Andrew S / Rosenberg, Stephen A / Wuthrick, Evan J

Cureus

2022 Volume 14, Issue 8, Page(s) e27558

Abstract: MRI-guided radiation therapy (MRgRT) enables real-time imaging during treatment and daily online adaptive planning. It is particularly useful for areas of treatment that have been previously excluded or restricted from ablative doses due to potential ... ...

Abstract	MRI-guided radiation therapy (MRgRT) enables real-time imaging during treatment and daily online adaptive planning. It is particularly useful for areas of treatment that have been previously excluded or restricted from ablative doses due to potential damage to adjacent normal tissue. In certain cases, ablative doses to metastatic lesions may be justified and treated with MRgRT using video-assisted gated breath-hold adjustments throughout delivery. The workflow relies on patient biofeedback and auditory cues. A 74-year-old deaf male with a history of prostate cancer status post prostatectomy was found to have an enlarged cervical lymph node, which was excised with histopathology demonstrating Merkel cell carcinoma. Approximately one year after treatment with two cycles of pembrolizumab, which was subsequently discontinued due to toxicity, surveillance imaging demonstrated an enlarging left adrenal nodule. It was initially stable for an additional seven months with pembrolizumab rechallenge but was again found enlarged on subsequent imaging. The patient underwent MRg stereotactic body radiation therapy (MRgSBRT) to a total dose of 60 Gy in five fractions to this isolated site of progression. The patient was equipped with mirrored glasses to view the tracking structure with respect to gating the boundary structure, and the traditional reliance on verbal cues for coaching was reimagined to rely on visual cues instead. Follow-up positron emission tomography/CT (PET/CT) two weeks after treatment demonstrated interval resolution of the left adrenal metastatic nodule and a return to symmetric bilateral adrenal gland metabolic activity. The necessary MRgSBRT treatment for single metastatic lesions near normal tissue structures relies on verbal cues and coaching. However, deaf patients are unable to receive this treatment according to the traditional workflow model. Unique opportunities exist for the implementation of culturally competent care for the Deaf community, relying more heavily on visual cues, in radiation oncology practice.
Language	English
Publishing date	2022-08-01
Publishing country	United States
Document type	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.27558
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Article ; Online: Magnetic Resonance-Guided Stereotactic Body Radiation Therapy/Hypofractionated Radiation therapy for Metastatic and Primary Central and Ultracentral Lung Lesions.

Sandoval, Maria L / Sim, Austin J / Bryant, John M / Bhandari, Menal / Wuthrick, Evan J / Perez, Bradford A / Dilling, Thomas J / Redler, Gage / Andreozzi, Jacqueline / Nardella, Louis / Feygelman, Vladimir / Latifi, Kujtim / Rosenberg, Stephen A

JTO clinical and research reports

2023 Volume 4, Issue 5, Page(s) 100488

Abstract: Introduction: The recent results from the Nordic-HILUS study indicate stereotactic body radiation therapy (SBRT) is associated with high-grade toxicity for ultracentral (UC) tumors. We hypothesized that magnetic resonance-guided SBRT (MRgSBRT) or ... ...

Abstract	Introduction: The recent results from the Nordic-HILUS study indicate stereotactic body radiation therapy (SBRT) is associated with high-grade toxicity for ultracentral (UC) tumors. We hypothesized that magnetic resonance-guided SBRT (MRgSBRT) or hypofractionated radiation therapy (MRgHRT) enables the safe delivery of high-dose radiation to central and UC lung lesions. Methods: Patients with UC or central lesions were treated with MRgSBRT/MRgHRT with real-time gating or adaptation. Central lesions were defined as per the Radiation Therapy Oncology Group and UC as per the HILUS study definitions: (1) group A or tumors less than 1 cm from the trachea and/or mainstem bronchi; or (2) group B or tumors less than 1 cm from the lobar bronchi. The Kaplan-Meier estimate and log-rank test were used to estimate survival. Associations between toxicities and other patient factors were tested using the Mann-Whitney Results: A total of 47 patients were included with a median follow-up of 22.9 months (95% confidence interval: 16.4-29.4). Most (53%) had metastatic disease. All patients had central lesions and 55.3% (n = 26) had UC group A. The median distance from the proximal bronchial tree was 6.0 mm (range: 0.0-19.0 mm). The median biologically equivalent dose (α/β = 10) was 105 Gy (range: 75-151.2). The most common radiation schedule was 60 Gy in eight fractions (40.4%). Most (55%) had previous systemic therapy, 32% had immunotherapy and 23.4% had previous thoracic radiation therapy. There were 16 patients who underwent daily adaptation. The 1-year overall survival was 82% (median = not reached), local control 87% (median = not reached), and progression-free survival 54% (median = 15.1 mo, 95% confidence interval: 5.1-25.1). Acute toxicity included grade 1 (26%) and grade 2 (21%) with only two patients experiencing grade 3 (4.3%) in the long term. No grade 4 or 5 toxicities were seen. Conclusions: Previous studies noted high rates of toxicity after SBRT to central and UC lung lesions, with reports of grade 5 toxicities. In our cohort, the use of MRgSBRT/MRgHRT with high biologically effective doses was well tolerated, with two grade 3 toxicities and no grade 4/5.
Language	English
Publishing date	2023-02-25
Publishing country	United States
Document type	Journal Article
ISSN	2666-3643
ISSN (online)	2666-3643
DOI	10.1016/j.jtocrr.2023.100488
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Article ; Online: Adjuvant Radiation Does Not Affect Locoregional Control Following Resection of Melanoma Satellitosis or In-Transit Disease.

Yaney, Alexander C / Rossfeld, Kara K / Wu, Trudy C / Agnese, Doreen M / Terando, Alicia M / Wuthrick, Evan J / Howard, John H

The American surgeon

2021 Volume 89, Issue 4, Page(s) 850–857

Abstract: Background: This study evaluates the association of adjuvant radiation therapy (RT) with improved locoregional (LR) recurrence for resected melanoma satellitosis and in-transit disease (ITD).: Materials and methods: Data were collected ... ...

Abstract	Background: This study evaluates the association of adjuvant radiation therapy (RT) with improved locoregional (LR) recurrence for resected melanoma satellitosis and in-transit disease (ITD). Materials and methods: Data were collected retrospectively for resected melanoma satellitosis/ITD from 1996 to 2017. Results: 99 patients were identified. 20 patients (20.2%) received adjuvant RT while 79 (79.8%) did not. Mean follow-up in the RT group was 4.3 years and 4.7 years in the non-RT group. 80% of patients who underwent RT suffered a complication, most commonly dermatitis. Locoregional recurrence occurred in 9 patients (45%) treated with adjuvant RT and 30 patients (38%) in the non-RT group ( Discussion: The use of adjuvant RT is not associated with improved locoregional control in resected melanoma satellitosis or ITD. Close or positive margin was the only treatment-related factor associated with decreased LR-DFS after surgical resection of satellitosis/ITD.
MeSH term(s)	Humans ; Radiotherapy, Adjuvant ; Retrospective Studies ; Neoplasm Recurrence, Local ; Melanoma/radiotherapy ; Melanoma/surgery
Language	English
Publishing date	2021-10-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	202465-2
ISSN	1555-9823 ; 0003-1348
ISSN (online)	1555-9823
ISSN	0003-1348
DOI	10.1177/00031348211047492
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Article: Yttrium-90 microsphere selective internal radiation therapy for liver metastases following systemic chemotherapy and surgical resection for metastatic adrenocortical carcinoma.

Makary, Mina S / Krishner, Lawrence S / Wuthrick, Evan J / Bloomston, Mark P / Dowell, Joshua D

World journal of clinical oncology

2017 Volume 9, Issue 1, Page(s) 20–25

Abstract: Adrenocortical carcinoma (ACC) is a rare malignancy with generally poor outcomes and limited treatment options. While surgical resection can be curative for early local disease, most patients present with advanced ACC owing to nonspecific symptoms. For ... ...

Abstract	Adrenocortical carcinoma (ACC) is a rare malignancy with generally poor outcomes and limited treatment options. While surgical resection can be curative for early local disease, most patients present with advanced ACC owing to nonspecific symptoms. For those patients, treatment options include systemic chemotherapy and locoregional therapies including radiofrequency ablation and transarterial chemoembolization. We present the first reported case of utilizing yttrium-90 microsphere selective internal radiation therapy (SIRT) in combination with first line EDP-M (Etoposide, Doxorubicin, Cisplatin, Mitotane) chemotherapy and debulking surgical primary tumor resection for treatment of metastatic ACC. Stable complete radiologic response has been maintained after twelve months with resolution of clinical symptoms. These findings prompt the need for further consideration and studies to elucidate the role of SIRT in combination with systemic and surgical treatment for metastatic ACC.
Language	English
Publishing date	2017-03-01
Publishing country	United States
Document type	Case Reports
ZDB-ID	2587357-X
ISSN	2218-4333
ISSN	2218-4333
DOI	10.5306/wjco.v9.i1.20
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Article ; Online: Clinical feasibility of

Wright, Chadwick L / Binzel, Katherine / Zhang, Jun / Wuthrick, Evan J / Knopp, Michael V

European journal of nuclear medicine and molecular imaging

2017 Volume 44, Issue 7, Page(s) 1194–1197

Abstract: Purpose: The purpose of this study was to evaluate the clinical feasibility of next generation solid-state digital photon counting PET/CT (dPET/CT) technology and imaging findings in patients following : Methods: Five patients underwent SOC : ... ...

Abstract	Purpose: The purpose of this study was to evaluate the clinical feasibility of next generation solid-state digital photon counting PET/CT (dPET/CT) technology and imaging findings in patients following Methods: Five patients underwent SOC Results: Digital PET/CT consistently provided better visual image quality and Conclusions: Digital PET/CT is clinically feasible for the assessment of
MeSH term(s)	Embolization, Therapeutic ; Feasibility Studies ; Humans ; Microspheres ; Positron Emission Tomography Computed Tomography ; Tissue Distribution ; Yttrium Radioisotopes/chemistry ; Yttrium Radioisotopes/therapeutic use
Chemical Substances	Yttrium Radioisotopes
Language	English
Publishing date	2017-07
Publishing country	Germany
Document type	Journal Article
ZDB-ID	8236-3
ISSN	1619-7089 ; 0340-6997 ; 1619-7070
ISSN (online)	1619-7089
ISSN	0340-6997 ; 1619-7070
DOI	10.1007/s00259-017-3694-4
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Article ; Online: Stereotactic radiosurgery and anti-PD-1 + CTLA-4 therapy, anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors, BRAF inhibitors, or conventional chemotherapy for the management of melanoma brain metastases.

Dohm, Ammoren E / Nakashima, Justyn Y / Kalagotla, Hruday / Jiang, Shirley X / Tang, Joseph D / Bhandari, Menal / Kim, Youngchul / Graham, Jasmine A / Khushalani, Nikhil I / Forsyth, Peter A / Etame, Arnold B / Liu, James K / Tran, Nam D / Vogelbaum, Michael A / Wuthrick, Evan J / Yu, Hsiang-Hsuan Michael / Oliver, Daniel E / Ahmed, Kamran A

European journal of cancer (Oxford, England : 1990)

2023 Volume 192, Page(s) 113287

Abstract: Background: Immunotherapy and targeted BRAF/MEK inhibitors (i) have revolutionised the systemic management of advanced melanoma. Given the role of stereotactic radiosurgery (SRS) in the local management of brain metastases, we sought to evaluate ... ...

Abstract	Background: Immunotherapy and targeted BRAF/MEK inhibitors (i) have revolutionised the systemic management of advanced melanoma. Given the role of stereotactic radiosurgery (SRS) in the local management of brain metastases, we sought to evaluate clinical outcomes in patients with melanoma brain metastases (MBM) treated with SRS and various systemic therapies. Methods: Patients were included if MBM were diagnosed and treated with SRS within 3 months of receiving anti-PD-1+CTLA-4 therapy, anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK-i, BRAF-i, or conventional chemotherapy. Comparisons between groups were made for overall survival (OS), distant MBM control, local MBM, systemic progression-free survival (sPFS), and neurotoxicity. Results: In total, 257 patients with 1048 MBM treated over 368 SRS sessions between 2011 and 2020 were identified. On MVA, treatment with anti-PD1+anti-CTLA-4, anti-PD-1, and BRAF/MEK-i improved distant intracranial control over conventional chemotherapy. No significant differences were noted in local control (LC) between groups (p = 0.78). Kaplan-Meier OS at 12 months for anti-PD-1 + CTLA-4 therapy, anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK-i, BRAF-i, and conventional chemotherapy was 68%, 59%, 45%, 62%, 21%, and 15%, respectively (p = <0.0001). The sPFS rates at 12 months were 57%, 53%, 42%, 45%, 14%, and 6% (p = <0.0001). No significant differences were noted in rates of radiation necrosis (p = 0.93). Conclusions: This is among the largest series evaluating MBM treated with SRS and various systemic therapy regimens. Our analysis noted significant differences in OS, distant MBM control, and sPFS by systemic therapy. No differences in LC or radiation necrosis risk were noted.
MeSH term(s)	Humans ; Proto-Oncogene Proteins B-raf/genetics ; Radiosurgery/adverse effects ; Brain Neoplasms/therapy ; Melanoma/therapy ; Protein Kinase Inhibitors/adverse effects ; Radiation Injuries ; Necrosis ; Mitogen-Activated Protein Kinase Kinases
Chemical Substances	Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; Protein Kinase Inhibitors ; Mitogen-Activated Protein Kinase Kinases (EC 2.7.12.2) ; BRAF protein, human (EC 2.7.11.1)
Language	English
Publishing date	2023-08-07
Publishing country	England
Document type	Journal Article
ZDB-ID	82061-1
ISSN	1879-0852 ; 0277-5379 ; 0959-8049 ; 0964-1947
ISSN (online)	1879-0852
ISSN	0277-5379 ; 0959-8049 ; 0964-1947
DOI	10.1016/j.ejca.2023.113287
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