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1
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Susman S, Santoso B, Makary MS. Locoregional Therapies for Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease. Biomedicines 2024; 12:2226. [PMID: 39457538 PMCID: PMC11504147 DOI: 10.3390/biomedicines12102226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Revised: 09/17/2024] [Accepted: 09/23/2024] [Indexed: 10/28/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide with an average five-year survival rate in the US of 19.6%. With the advent of HBV and HCV treatment and prevention, along with the rising rates of obesity, nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome are set to overtake infectious causes as the most common cause of HCC. While surgical resection and transplantation can be curative when amenable, the disease is most commonly unresectable on presentation, and other treatment approaches are the mainstay of therapy. In these patients, locoregional therapies have evolved as a vital tool in both palliation for advanced disease and as a bridge to surgical resection and transplantation. In this review, we will be exploring the primary locoregional therapies for HCC in patients with NAFLD, including transarterial chemoembolization (TACE), bland transarterial embolization (TAE), transarterial radioembolization (TARE), and percutaneous ablation.
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Affiliation(s)
- Stephen Susman
- Department of Radiology, Yale University Medical Center, New Haven, CT 06510, USA
| | - Breanna Santoso
- Heritage College of Osteopathic Medicine, Ohio University, Dublin, OH 43016, USA
| | - Mina S. Makary
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43202, USA
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2
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Bajestani N, Wu G, Hussein A, Makary MS. Examining the Efficacy and Safety of Combined Locoregional Therapy and Immunotherapy in Treating Hepatocellular Carcinoma. Biomedicines 2024; 12:1432. [PMID: 39062006 PMCID: PMC11274263 DOI: 10.3390/biomedicines12071432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 06/14/2024] [Accepted: 06/21/2024] [Indexed: 07/28/2024] Open
Abstract
More than 800,000 people worldwide are diagnosed with HCC (hepatocellular carcinoma) each year, with approximately 700,000 deaths alone occurring in that same year. Treatment of HCC presents complex therapeutic challenges, particularly in intermediate and advanced stages. LRTs such as transarterial chemoembolization (TACE) and ablations have been the mainstay treatment for early to intermediate-stage HCC, and systemic therapies are used to treat intermediate-late-stage HCC. However, novel literature describing combining LRT with systemic therapies has shown promising results. This review explores recent advances in both liver-directed techniques for hepatocellular carcinoma, including bland transarterial embolization, chemoembolization, radioembolization, and ablative therapies in conjunction as well as with systemic therapies, with a focus on combination therapies, patient selection, procedural technique, periprocedural management, and outcomes. Our findings suggest that LRT combined with systemic therapies is a viable strategy for improving progression-free survival and time to progression for patients with intermediate-to-late-stage HCC. However, further investigation is required to refine treatment protocols and define patient cohorts that would benefit the most.
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Affiliation(s)
- Nojan Bajestani
- College of Medicine, The Ohio State University, Columbus, OH 43210, USA; (G.W.); (A.H.)
| | - Gavin Wu
- College of Medicine, The Ohio State University, Columbus, OH 43210, USA; (G.W.); (A.H.)
| | - Ahmed Hussein
- College of Medicine, The Ohio State University, Columbus, OH 43210, USA; (G.W.); (A.H.)
| | - Mina S. Makary
- Division of Vascular and Interventional Radiology, Department of Radiology, The Ohio State University Wexner Medical Center, 395 W 12th Avenue, Columbus, OH 43210, USA;
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3
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Makary MS, Bozer J, Miller ED, Diaz DA, Rikabi A. Long-term Clinical Outcomes of Yttrium-90 Transarterial Radioembolization for Hepatocellular Carcinoma: A 5-Year Institutional Experience. Acad Radiol 2024; 31:1828-1835. [PMID: 37537129 DOI: 10.1016/j.acra.2023.07.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Revised: 07/08/2023] [Accepted: 07/09/2023] [Indexed: 08/05/2023]
Abstract
RATIONALE AND OBJECTIVES To examine the clinical outcomes of yttrium-90 (Y90) transarterial radioembolization (TARE) for primary hepatocellular carcinoma (HCC) through the evaluation of a 5-year institutional experience. MATERIALS AND METHODS This retrospective study evaluated 88 consecutive patients with primary HCC receiving Y90 TARE treatment at an academic medical center from 2017 to 2021. Disease distribution was bilobar in 60.2% of patients with an average lesion diameter of 5.0 ± 3.4 cm and Barcelona Clinic Liver Cancer stage B or C in 77% of the participants. Clinical outcomes were elucidated by examination of complications, liver function tests, biochemical response, and radiographic response. Objective response ratio (ORR) and progression-free survival (PFS) were also calculated. RESULTS The mean administered Y90 radiation dose was 127.8 ± 20.2 Gy. No significant complications or LFT elevations occurred post-therapy. Of the 73.9% of patients with α-fetoprotein-producing tumors, 67.8% experienced a complete or partial biochemical response 1 month post-treatment. The ORR was 83.3% on 6-month imaging and PFS was 9.6 ± 8.5 months. Functional outcomes (Eastern Cooperative Oncology Group) were maintained or improved in 79.6% and 76.1% of patients by 6 months and 1 year post-treatment, respectively. The mean survival was 14.7 ± 12.1 months. At 6 months post-treatment, 77.3% of patients were downstaged to or maintained Milan criteria, which was sustained for 74.4% and 70.0% of patients 1 year and 2 years after treatment, respectively. CONCLUSION Y90-TARE is a safe and effective therapy for primary HCC. Enduring outcomes further act as a realistic bridge to liver transplantation, with a majority of patients maintaining Milan criteria and preserving their functional status long term.
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Affiliation(s)
- Mina S Makary
- Division of Vascular and Interventional Radiology, Department of Radiology, The Ohio State University Wexner Medical Center, 395 W 12th Avenue, 4th Floor, Columbus, OH 43210 (M.S.M., J.B., A.R.).
| | - Jordan Bozer
- Division of Vascular and Interventional Radiology, Department of Radiology, The Ohio State University Wexner Medical Center, 395 W 12th Avenue, 4th Floor, Columbus, OH 43210 (M.S.M., J.B., A.R.)
| | - Eric D Miller
- Department of Radiation Oncology, The Ohio State University Medical Center, Columbus, Ohio (E.D.M., D.A.D.)
| | - Dayssy A Diaz
- Department of Radiation Oncology, The Ohio State University Medical Center, Columbus, Ohio (E.D.M., D.A.D.)
| | - Ali Rikabi
- Division of Vascular and Interventional Radiology, Department of Radiology, The Ohio State University Wexner Medical Center, 395 W 12th Avenue, 4th Floor, Columbus, OH 43210 (M.S.M., J.B., A.R.)
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4
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Kimpel O, Altieri B, Laganà M, Vogl TJ, Adwan H, Dusek T, Basile V, Pittaway J, Dischinger U, Quinkler M, Kroiss M, Puglisi S, Cosentini D, Kickuth R, Kastelan D, Fassnacht M. The Value of Local Therapies in Advanced Adrenocortical Carcinoma. Cancers (Basel) 2024; 16:706. [PMID: 38398097 PMCID: PMC10886520 DOI: 10.3390/cancers16040706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 01/23/2024] [Accepted: 02/01/2024] [Indexed: 02/25/2024] Open
Abstract
International guidelines recommend local therapies (LTs) such as local thermal ablation (LTA; radiofrequency, microwave, cryoablation), transarterial (chemo)embolisation (TA(C)E), and transarterial radioembolisation (TARE) as therapeutic options for advanced adrenocortical carcinoma (ACC). However, the evidence for these recommendations is scarce. We retrospectively analysed patients receiving LTs for advanced ACC. Time to progression of the treated lesion (tTTP) was the primary endpoint. The secondary endpoints were best objective response, overall progression-free survival, overall survival, adverse events, and the establishment of predictive factors by multivariate Cox analyses. A total of 132 tumoural lesions in 66 patients were treated with LTA (n = 84), TA(C)E (n = 40), and TARE (n = 8). Complete response was achieved in 27 lesions (20.5%; all of them achieved by LTA), partial response in 27 (20.5%), and stable disease in 38 (28.8%). For the LTA group, the median tTTP was not reached, whereas it was reached 8.3 months after TA(C)E and 8.2 months after TARE (p < 0.001). The median time interval from primary diagnosis to LT was >47 months. Fewer than four prior therapies and mitotane plasma levels of >14 mg/L positively influenced the tTTP. In summary, this is one of the largest studies on LTs in advanced ACC, and it demonstrates a very high local disease control rate. Thus, it clearly supports the guideline recommendations for LTs in these patients.
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Affiliation(s)
- Otilia Kimpel
- Division of Endocrinology and Diabetes, Department of Medicine, University Hospital, University of Würzburg, 97070 Würzburg, Germany; (B.A.); (U.D.); (M.K.); (M.F.)
| | - Barbara Altieri
- Division of Endocrinology and Diabetes, Department of Medicine, University Hospital, University of Würzburg, 97070 Würzburg, Germany; (B.A.); (U.D.); (M.K.); (M.F.)
| | - Marta Laganà
- Medical Oncology Unit, Department of Medical & Surgical Specialties, Radiological Sciences & Public Health, University of Brescia, ASST Spedali Civili of Brescia, 25123 Brescia, Italy; (M.L.); (D.C.)
| | - Thomas J. Vogl
- Universitätsklinikum Frankfurt, Institut für Diagnostische und Interventionelle Radiologie, 60596 Frankfurt, Germany; (T.J.V.)
| | - Hamzah Adwan
- Universitätsklinikum Frankfurt, Institut für Diagnostische und Interventionelle Radiologie, 60596 Frankfurt, Germany; (T.J.V.)
| | - Tina Dusek
- Department of Endocrinology, University Hospital Centre Zagreb, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia; (T.D.); (D.K.)
| | - Vittoria Basile
- Internal Medicine 1, San Luigi Gonzaga Hospital, Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; (V.B.); (S.P.)
| | - James Pittaway
- Department of Endocrinology, St Bartholomew’s Hospital, London EC1A 7BE, UK;
| | - Ulrich Dischinger
- Division of Endocrinology and Diabetes, Department of Medicine, University Hospital, University of Würzburg, 97070 Würzburg, Germany; (B.A.); (U.D.); (M.K.); (M.F.)
| | | | - Matthias Kroiss
- Division of Endocrinology and Diabetes, Department of Medicine, University Hospital, University of Würzburg, 97070 Würzburg, Germany; (B.A.); (U.D.); (M.K.); (M.F.)
- Department of Medicine IV, University Hospital, LMU Munich, Ziemssenstraße 1, 80336 München, Germany
| | - Soraya Puglisi
- Internal Medicine 1, San Luigi Gonzaga Hospital, Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; (V.B.); (S.P.)
| | - Deborah Cosentini
- Medical Oncology Unit, Department of Medical & Surgical Specialties, Radiological Sciences & Public Health, University of Brescia, ASST Spedali Civili of Brescia, 25123 Brescia, Italy; (M.L.); (D.C.)
| | - Ralph Kickuth
- Institute of Diagnostic and Interventional Radiology, University-Hospital of Würzburg, 97080 Würzburg, Germany;
| | - Darko Kastelan
- Department of Endocrinology, University Hospital Centre Zagreb, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia; (T.D.); (D.K.)
| | - Martin Fassnacht
- Division of Endocrinology and Diabetes, Department of Medicine, University Hospital, University of Würzburg, 97070 Würzburg, Germany; (B.A.); (U.D.); (M.K.); (M.F.)
- Comprehensive Cancer Center Mainfranken, University of Würzburg, 97070 Würzburg, Germany
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Mihai R, De Crea C, Guerin C, Torresan F, Agcaoglu O, Simescu R, Walz MK. Surgery for advanced adrenal malignant disease: recommendations based on European Society of Endocrine Surgeons consensus meeting. Br J Surg 2024; 111:znad266. [PMID: 38265812 PMCID: PMC10805373 DOI: 10.1093/bjs/znad266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Accepted: 08/02/2023] [Indexed: 01/25/2024]
Affiliation(s)
- Radu Mihai
- Churchill Cancer Centre, Oxford University Hospital NHS Foundation Trust, Oxford, UK
| | - Carmela De Crea
- Centro di Ricerca in Chirurgia delle Ghiandole Endocrine e dell’Obesità, Università Cattolica del Sacro Cuore, Rome, Italy
- Endocrine Surgery Unit, Hospital Fatebenefratelli Isola Tiberina—Gemelli Isola, Rome, Italy
| | - Carole Guerin
- Department of Endocrine and Metabolic Surgery, Aix-Marseille University, Hôpital de La Conception, Marseille, France
| | - Francesca Torresan
- Endocrine Surgery Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Orhan Agcaoglu
- Department of General Surgery, Koc University School of Medicine, Istanbul, Turkey
| | - Razvan Simescu
- Department of General and Endocrine Surgery, Medlife-Humanitas Hospital, Cluj-Napoca, Romania
| | - Martin K Walz
- Department of Surgery and Minimally Invasive Surgery, Kliniken Essen-Mitte, Essen, Germany
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6
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Hare AE, Makary MS. Locoregional Approaches in Cholangiocarcinoma Treatment. Cancers (Basel) 2022; 14:5853. [PMID: 36497334 PMCID: PMC9740081 DOI: 10.3390/cancers14235853] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 11/20/2022] [Accepted: 11/24/2022] [Indexed: 11/29/2022] Open
Abstract
Cholangiocarcinoma (CCA) is a rare hepatic malignant tumor with poor prognosis due to late detection and anatomic factors limiting the applicability of surgical resection. Without surgical resection, palliation is the most common approach. In non-surgical cases contained within the liver, locoregional therapies provide the best chance for increased survival and disease control. The most common methods, transarterial chemoembolization and transarterial radioembolization, target tumors by embolizing their blood supply and limiting the tumor's ability to metabolize. Other treatments induce direct damage via thermal ablation to tumor tissue to mediate their anti-tumor efficacy. Recent studies have begun to explore roles for these therapies outside their previous role of palliation. This review will outline the mechanisms of each of these treatments, along with their effects on overall survival, while comparing these to non-locoregional therapies.
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Affiliation(s)
| | - Mina S. Makary
- Division of Vascular and Interventional Radiology, Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
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7
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Lin TY, Lin KY, Kuo HY, Huang KH, Wang CY, Lin YL, Shih SR, Liang PC. Yttrium-90 Selective Internal Radiation Therapy Plus Cryoablation for Recurrent Adrenocortical Carcinoma With Liver Metastases. J Endocr Soc 2022; 6:bvac091. [PMID: 35795808 PMCID: PMC9249972 DOI: 10.1210/jendso/bvac091] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Indexed: 11/29/2022] Open
Abstract
Advanced adrenocortical carcinoma (ACC) has a poor prognosis and is often resistant to the conventional regimens of mitotane administration and systemic chemotherapy. In addition to surgery, local therapeutic measures can be valuable. Here, we present the case of a 33-year-old woman who developed left retroperitoneal local recurrent ACC with hepatic and pulmonary metastases 1 year after radical adrenalectomy. The tumors progressed under chemotherapy and mitotane treatments. She was treated with yttrium-90 selective internal radiation therapy (90Y SIRT) for hepatic metastases and cryoablation of the local recurrent tumor, after which significant tumor shrinkage was observed. She then received radiofrequency ablation for the residual hepatic metastases and radiotherapy to the residual local recurrent tumor. Complete remission was achieved and maintained at least until the data cutoff day (15.8 months after the last treatment). This is the first published report of cryoablation in a patient with ACC and the third report of 90Y SIRT use for hepatic metastasis of ACC. Cryoablation and 90Y SIRT are local treatment choices for ACC that are worthy of further study.
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Affiliation(s)
- Tung-Yen Lin
- Department of Internal Medicine, National Taiwan University Hospital , Taipei , Taiwan
| | - Kuan-Yu Lin
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital , Taipei , Taiwan
| | - Hung-Yang Kuo
- Division of Hematology and Oncology, Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch , Hsin-Chu , Taiwan
| | - Kuo-How Huang
- Department of Urology, National Taiwan University Hospital , Taipei , Taiwan
| | - Chih-Yuan Wang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital , Taipei , Taiwan
| | - Yu-Lin Lin
- Department of Oncology, National Taiwan University Hospital , Taipei , Taiwan
- Graduate Institute of Oncology, National Taiwan University College of Medicine , Taipei , Taiwan
| | - Shyang-Rong Shih
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital , Taipei , Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine , Taipei , Taiwan
- Center of Anti-Aging and Health Consultation, National Taiwan University Hospital , Taipei , Taiwan
| | - Po-Chin Liang
- Department of Medical Imaging, National Taiwan University Hospital Hsin-Chu Branch , Taiwan
- Department of Medical Imaging, National Taiwan University Hospital , Taipei 100 , Taiwan
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8
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Makary MS, Ramsell S, Miller E, Beal EW, Dowell JD. Hepatocellular carcinoma locoregional therapies: Outcomes and future horizons. World J Gastroenterol 2021; 27:7462-7479. [PMID: 34887643 PMCID: PMC8613749 DOI: 10.3748/wjg.v27.i43.7462] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 07/09/2021] [Accepted: 10/27/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver and has an overall five-year survival rate of less than twenty percent. For patients with unresectable disease, evolving liver-directed locoregional therapies provide efficacious treatment across the spectrum of disease stages and via a variety of catheter-directed and percutaneous techniques. Goals of locoregional therapies in HCC may include curative intent in early-stage disease, bridging or downstaging to surgical resection or transplantation for early or intermediate-stage disease, and local disease control and palliation in advanced-stage disease. This review explores the outcomes of chemoembolization, bland embolization, radioembolization, and percutaneous ablative therapies. Attention is also given to prognostic factors related to each of the respective techniques, as well as future directions of locoregional therapies for HCC.
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Affiliation(s)
- Mina S Makary
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Stuart Ramsell
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Eric Miller
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Eliza W Beal
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Joshua D Dowell
- Department of Radiology, Northwest Radiology, St. Vincent Health, Indianapolis, IN 46260, United States
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Zane KE, Cloyd JM, Mumtaz KS, Wadhwa V, Makary MS. Metastatic disease to the liver: Locoregional therapy strategies and outcomes. World J Clin Oncol 2021; 12:725-745. [PMID: 34631439 PMCID: PMC8479345 DOI: 10.5306/wjco.v12.i9.725] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 06/14/2021] [Accepted: 08/31/2021] [Indexed: 02/06/2023] Open
Abstract
Secondary cancers of the liver are more than twenty times more common than primary tumors and are incurable in most cases. While surgical resection and systemic chemotherapy are often the first-line therapy for metastatic liver disease, a majority of patients present with bilobar disease not amenable to curative local resection. Furthermore, by the time metastasis to the liver has developed, many tumors demonstrate a degree of resistance to systemic chemotherapy. Fortunately, catheter-directed and percutaneous locoregional approaches have evolved as major treatment modalities for unresectable metastatic disease. These novel techniques can be used for diverse applications ranging from curative intent for small localized tumors, downstaging of large tumors for resection, or locoregional control and palliation of advanced disease. Their use has been associated with increased tumor response, increased disease-free and overall survival, and decreased morbidity and mortality in a broad range of metastatic disease. This review explores recent advances in liver-directed therapies for metastatic liver disease from primary colorectal, neuroendocrine, breast, and lung cancer, as well as uveal melanoma, cholangiocarcinoma, and sarcoma. Therapies discussed include bland transarterial embolization, chemoembolization, radioembolization, and ablative therapies, with a focus on current treatment approaches, outcomes of locoregional therapy, and future directions in each type of metastatic disease.
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Affiliation(s)
- Kylie E Zane
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Jordan M Cloyd
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Khalid S Mumtaz
- Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Vibhor Wadhwa
- Department of Radiology, Weill Cornell Medical Center, New York City, NY 10065, United States
| | - Mina S Makary
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
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Mauda-Havakuk M, Levin E, Levy EB, Krishnasamy VP, Anderson V, Jain N, Amalou H, Fojo T, Edgerly M, Wakim PG, Hughes MS, Del Rivero J, Wood BJ. Long-term outcomes in patients with advanced adrenocortical carcinoma after image-guided locoregional ablation or embolization. Cancer Med 2021; 10:2259-2267. [PMID: 33687146 PMCID: PMC7982621 DOI: 10.1002/cam4.3740] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 12/14/2020] [Accepted: 12/17/2020] [Indexed: 12/31/2022] Open
Abstract
Background To evaluate outcomes and survival rates in patients with metastatic adrenocortical carcinoma (ACC) who were treated with image‐guided locoregional treatments (IGLTs). Purpose To evaluate the overall survival (OS) and clinical impact of IGLT in the management of patients with advanced metastatic ACC. Methods Retrospective review of 39 patients treated with IGLT between 1999 and 2018 was performed. Short‐ and long‐term efficacy of treatments were defined based upon imaging and clinical data. Subgroup survival analysis was performed on patients with metastatic disease at diagnosis (N = 17) and compared with the same stage group from the most recent National Cancer Database (NCDB) report. Statistical analysis was performed using Cox proportional hazards model. Results Treatments were performed at different anatomic sites including liver (N = 46), lung (N = 14), retroperitoneum (N = 5), bone (N = 4), subcutaneous (N = 2), and intracaval (N = 1). Radiofrequency, microwave, cryoablation, or a combination of two modalities (45, 18, 3, 3, respectively) were used in 69 ablation sessions. Intra‐arterial procedures were performed in 12 patients in 18 treatment cycles (range 1–3 per patient). As of a 2019 analysis, 11 patients were alive with a mean follow‐up of 169 months (range 63–292 months) from diagnosis. Two‐ and 5‐year OS rates for all patients were 84.5% and 51%, respectively, and 76.5% and 59% for patients with metastatic disease at diagnosis (N = 17). This compares favorably with an NCDB report of 35% 5‐year survival rate for patients with metastatic disease. Female gender and longer time from diagnosis to first IGLT were found to be predictors of prolonged survival with hazard ratios of 0.23 (p < 0.001) and 0.66 (p = 0.001), respectively. Conclusion IGLT may be associated with prolonged life expectancy in select patients with metastatic ACC.
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Affiliation(s)
- Michal Mauda-Havakuk
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, and the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA
| | - Elizabeth Levin
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Elliot B Levy
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Venkatesh P Krishnasamy
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Victoria Anderson
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Nidhi Jain
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Hayet Amalou
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Tito Fojo
- Division of Medical Oncology, Department of Medicine, Columbia University Medical Center, New York, NY, USA
| | - Maureen Edgerly
- Office of Research Nursing Center for Cancer Research National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Paul G Wakim
- Biostatistics and Clinical Epidemiology Service, National Institutes of Health Clinical Center, Bethesda, MD, USA
| | - Marybeth S Hughes
- Surgical Oncology, Eastern Virginia Medical School, Norfolk, VA, USA
| | - Jaydira Del Rivero
- Developmental Therapeutics Branch, Medical Oncology Service, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Bradford J Wood
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institute of Biomedical Imaging and Bioengineering and National Cancer Institute Center for Cancer Research, National Institutes of Health, Bethesda, MD, USA
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11
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Lu S, Dhillon J, Johnson JH, El-Haddad G. Yttrium-90 radioembolization of isolated hepatic adrenocortical carcinoma metastases with negative surgical pathology. EJNMMI Res 2021; 11:17. [PMID: 33604708 PMCID: PMC7892660 DOI: 10.1186/s13550-021-00755-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Accepted: 02/01/2021] [Indexed: 12/14/2022] Open
Abstract
Background Adrenocortical carcinoma (ACC) is an uncommon malignancy with an estimated 15,400 new cases annually across the globe. The prognosis is generally poor as the disease is often already advanced at initial diagnosis due to non-specific symptoms. Even for local disease, recurrence after surgical resection is high. Treatment choices for advanced disease include mitotane, chemotherapy, ablation, chemoembolization, radioembolization, and external beam radiotherapy, with varying degrees of efficacy. To the best of our knowledge, there have only been two prior case studies of complete clinical and radiological response of stage 4 disease at 1 year and 2 years after yttrium-90 (90Y) microsphere selective internal radiation therapy (SIRT) of isolated hepatic metastases post-surgery and chemotherapy. Case presentation We present a case of a 58-year-old man with metastatic ACC who was treated with 90Y resin microsphere (SIR-spheres) for local control of liver metastases leading to a surgically proven negative pathology after partial hepatectomy 7 months after SIRT. The patient was initially diagnosed with stage 1 ACC that progressed 6 years later to stage 4 disease with new liver metastases that were deemed unresectable at an outside institution. After review of the case at multidisciplinary tumor board, he was referred for liver directed therapy for local tumor control. Angiographic workup demonstrated partial extrahepatic supply to the tumors from the right inferior phrenic artery, which was successfully embolized on the day of SIRT for flow redistribution. As the patient was being treated with mitotane that suppresses steroid production, he developed post-SIRT adrenal crisis, which was successfully controlled with steroids, highlighting the need for pre SIRT stress dose steroids. Conclusions This case continues to add to the literature supporting 90Y radioembolization as an effective treatment for isolated hepatic ACC metastases. Our case is the first to demonstrate surgically proven negative pathology after radioembolization. Further prospective study is warranted to better establish efficacy as well as safety of SIRT for ACC liver metastases.
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Affiliation(s)
- Sen Lu
- Department of Diagnostic and Interventional Radiology, University of South Florida, 2 Tampa General Circle, STC 7028, Tampa, FL, 33606, USA.
| | - Jasreman Dhillon
- Department of Pathology, Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL, 33612, USA
| | - Julie Hallanger Johnson
- Department of Endocrinology, Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL, 33612, USA
| | - Ghassan El-Haddad
- Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL, 33612, USA
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Ardolino L, Hansen A, Ackland S, Joshua A. Advanced Adrenocortical Carcinoma (ACC): a Review with Focus on Second-Line Therapies. HORMONES & CANCER 2020; 11:155-169. [PMID: 32303972 PMCID: PMC10355245 DOI: 10.1007/s12672-020-00385-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Accepted: 04/01/2020] [Indexed: 02/07/2023]
Abstract
Advanced adrenocortical cancer (ACC) is a rare, highly aggressive malignancy, which typically has a poor prognosis. In advanced ACC, the overall trend is toward a short PFS interval following first-line systemic therapy, highlighting a clear need for improved second-/third-line treatment strategies. We conducted a review of the literature and relevant scientific guidelines related to systemic therapy for advanced ACC. Public indexes including PubMed/MEDLINE were searched. Treatment selection in the second-line setting is based on small phase 2 trials, case reports, and pre-clinical evidence. The best data available for initial second-line therapy selection supports the use of gemcitabine and capecitabine (G + C) or streptozotocin (S), both with or without mitotane. G + C is becoming increasingly recommended based on phase 2 clinical trial data in patients of good PS, due to the inferred superior PFS and OS from non-comparative trials. Alternatively, streptozotocin was better tolerated than EDP + M in the FIRM-ACT study and remains an option when warranted. Beyond this, further treatment approaches should be tailored to individual patient characteristics, utilizing a mixture of systemic therapies, local therapies, and enrolment in clinical trials where available. Additionally, the role of molecular stratification, predictive biomarkers, and immune checkpoint inhibitors in specific individuals, such as Lynch syndrome, is evolving and may become increasingly utilized in clinical practice. Advanced ACC necessitates a multidisciplinary approach and is best managed in a specialist center. Although there is no one definitive second-line treatment strategy, there are some favorable approaches, which require further validation in larger clinical trials.
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Affiliation(s)
- Luke Ardolino
- The Kinghorn Cancer Centre, St. Vincent's Hospital, Sydney, NSW, Australia.
| | - Aaron Hansen
- Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
| | - Stephen Ackland
- Calvary Mater Newcastle Hospital, University of Newcastle, Newcastle, NSW, Australia
| | - Anthony Joshua
- The Kinghorn Cancer Centre, St. Vincent's Hospital, Sydney, NSW, Australia
- St. Vincent's Clinical School, UNSW, Sydney, NSW, Australia
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Makary MS, Khandpur U, Cloyd JM, Mumtaz K, Dowell JD. Locoregional Therapy Approaches for Hepatocellular Carcinoma: Recent Advances and Management Strategies. Cancers (Basel) 2020; 12:1914. [PMID: 32679897 PMCID: PMC7409274 DOI: 10.3390/cancers12071914] [Citation(s) in RCA: 89] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 07/12/2020] [Accepted: 07/14/2020] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and third leading cause of cancer-related mortality worldwide. While surgical resection and transplantation are the standard first-line treatments for early-stage HCC, most patients do not fulfill criteria for surgery. Fortunately, catheter-directed and percutaneous locoregional approaches have evolved as major treatment modalities for unresectable HCC. Improved outcomes have been achieved with novel techniques which can be employed for diverse applications ranging from curative-intent for small localized tumors, to downstaging or bridging to resection and transplantation for early and intermediate disease, and locoregional control and palliation for advanced disease. This review explores recent advances in liver-directed techniques for HCC including bland transarterial embolization, chemoembolization, radioembolization, and ablative therapies, with a focus on patient selection, procedural technique, periprocedural management, and outcomes.
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Affiliation(s)
- Mina S. Makary
- Division of Vascular and Interventional Radiology, Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA;
| | - Umang Khandpur
- Division of Vascular and Interventional Radiology, Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA;
| | - Jordan M. Cloyd
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA;
| | - Khalid Mumtaz
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA;
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Pigg N, Aboubechara D, Fourzali R, Baigorri B. Yttrium-90 Radioembolization of Metastatic Adrenocortical Carcinoma to the Liver following Systemic Chemotherapy and Surgical Resection of the Primary Lesion. Case Rep Oncol 2020; 13:158-163. [PMID: 32231538 DOI: 10.1159/000504779] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Accepted: 11/12/2019] [Indexed: 01/12/2023] Open
Abstract
Use of yttrium-90 (Y-90) is used for primary liver tumors and a handful of liver metastatic lesions. Y-90 treatment for metastatic adrenocortical carcinoma (ACC) to the liver is currently off-label, with one previously documented case report. In this case report, we present a 52-year-old woman with ACC and extensive liver metastatic disease. After failed chemotherapy, multidisciplinary discussion suggested potential Y-90 treatment for palliative purposes. After undergoing Y-90 treatment separately to the right and then the left hepatic lobes, subsequent patient visits demonstrated significantly improved clinical function as well as complete radiographic resolution of liver metastatic disease mainly from ACC. This case report demonstrates the potential efficacy of Y-90 for off-label uses in liver metastatic disease. This case and similar cases may open the door to a wide variety of potential indications for Y-90 treatment.
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Affiliation(s)
- Nicholas Pigg
- Department of Radiology, Aventura Hospital and Medical Center, Aventura, Florida, USA
| | - Daniel Aboubechara
- Department of Radiology, Aventura Hospital and Medical Center, Aventura, Florida, USA
| | - Roberto Fourzali
- Department of Radiology, Aventura Hospital and Medical Center, Aventura, Florida, USA
| | - Brian Baigorri
- Department of Radiology, Aventura Hospital and Medical Center, Aventura, Florida, USA
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