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Cocozza MA, Dajti E, Braccischi L, Modestino F, Reimer P, Cucchetti A, Barbara G, Mosconi C. Survival After Transarterial Radioembolization in Patients with Unresectable Intrahepatic Cholangiocarcinoma: An Updated Meta-analysis and Meta-regression. Cardiovasc Intervent Radiol 2024; 47:1313-1324. [PMID: 39187651 PMCID: PMC11486776 DOI: 10.1007/s00270-024-03825-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Accepted: 07/25/2024] [Indexed: 08/28/2024]
Abstract
PURPOSE Transarterial radioembolization (TARE) has emerged as a promising therapeutic approach for unresectable intrahepatic cholangiocarcinoma (ICCA). We updated our previous meta-analysis with meta-regression to explore the efficacy of TARE in the context of ICCA. METHODS We searched PubMed and Scopus for studies published up to September 1, 2023. The primary outcome was overall survival. Secondary outcomes were tumor overall response rate, severe adverse events, and downstaging to surgery. Meta-analysis employed a random-effects model, and meta-regression was utilized to explore sources of heterogeneity. RESULTS We included 27 studies, involving 1365 patients. Pooled survival estimates at 1, 2, and 3 years were 52.6%, 27%, and 16.8%, respectively. Meta-regression revealed that the proportion of patients naïve to treatment was the only pre-TARE predictor of survival (1-, 2-, and 3-year survival of 70%, 45%, and 36% for treatment-naïve patients, mean survival 19.7 months vs. 44%, 18%, and 7% for non-naïve patients, mean survival 12.2 months). Overall response according to RECIST 1.1 and mRECIST was 19.6% and 67%, respectively. Effective downstaging to surgery was possible in varying rates (3-54%); the mean survival in these patients was 34.8 months (1-, 2-, and 3-year survival of 100%, 87%, and 64%). About 45.7% of patients experienced adverse events, but only 5.9% were severe. CONCLUSIONS Our study benchmarked the survival rates of patients undergoing TARE for unresectable ICCA and showed that this is a valid option in these patients, especially if naïve to previous treatments. Downstaging to surgery is feasible in selected patients with promising results.
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Affiliation(s)
- Maria Adriana Cocozza
- Division of Interventional Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Elton Dajti
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
| | - Lorenzo Braccischi
- Division of Interventional Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Francesco Modestino
- Division of Interventional Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Peter Reimer
- Department of General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
| | - Alessandro Cucchetti
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
- Städtisches Klinikum Karlsruhe, Institute for Diagnostic and Interventional Radiology, Academic Teaching Hospital the University of Freiburg, Moltkestraße 90, 76133, Karlsruhe, Germany
| | - Giovanni Barbara
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Cristina Mosconi
- Division of Interventional Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
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Wagemans MEHM, Kunnen B, Stella M, van Rooij R, Smits M, Bruijnen R, Lam MGEH, de Jong HWAM, Braat AJAT. Comparison of 3 Different Therapeutic Particles in Radioembolization of Locally Advanced Intrahepatic Cholangiocarcinoma. J Nucl Med 2024; 65:272-278. [PMID: 38176716 DOI: 10.2967/jnumed.123.265597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 11/07/2023] [Indexed: 01/06/2024] Open
Abstract
Our objective was to compare 3 different therapeutic particles used for radioembolization in locally advanced intrahepatic cholangiocarcinoma. Methods: 90Y-glass, 90Y-resin, and 166Ho-labeled poly(l-lactic acid) microsphere prescribed activity was calculated as per manufacturer recommendations. Posttreatment quantitative 90Y PET/CT and quantitative 166Ho SPECT/CT were used to determine tumor-absorbed dose, whole-normal-liver-absorbed dose, treated-normal-liver-absorbed dose, tumor-to-nontumor ratio, lung-absorbed dose, and lung shunt fraction. Response was assessed using RECIST 1.1 and the [18F]FDG PET-based change in total lesion glycolysis. Hepatotoxicity was assessed using the radioembolization-induced liver disease classification. Results: Six 90Y-glass, 8 90Y-resin, and 7 166Ho microsphere patients were included for analysis. The mean administered activity was 2.6 GBq for 90Y-glass, 1.5 GBq for 90Y-resin, and 7.0 GBq for 166Ho microspheres. Tumor-absorbed dose and treated-normal-liver-absorbed dose were significantly higher for 90Y-glass than for 90Y-resin and 166Ho microspheres (mean tumor-absorbed dose, 197 Gy for 90Y-glass vs. 73 Gy for 90Y-resin and 50 Gy for 166Ho; mean treated-normal-liver-absorbed dose, 79 Gy for 90Y-glass vs. 37 Gy for 90Y-resin and 31 Gy for 166Ho). The whole-normal-liver-absorbed dose and tumor-to-nontumor ratio did not significantly differ between the particles. All patients had a lung-absorbed dose under 30 Gy and a lung shunt fraction under 20%. The 3 groups showed similar toxicity and response according to RECIST 1.1 and [18F]FDG PET-based total lesion glycolysis changes. Conclusion: The therapeutic particles used for radioembolization differed from each other and showed significant differences in absorbed dose, whereas toxicity and response were similar for all groups. This finding emphasizes the need for separate dose constraints and dose targets for each particle.
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Affiliation(s)
- Martijn E H M Wagemans
- Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands; and
| | - Britt Kunnen
- Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands; and
- Image Sciences Institute, UMC Utrecht and University Utrecht, Utrecht, The Netherlands
| | - Martina Stella
- Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands; and
| | - Rob van Rooij
- Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands; and
| | - Maarten Smits
- Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands; and
| | - Rutger Bruijnen
- Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands; and
| | - Marnix G E H Lam
- Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands; and
| | - Hugo W A M de Jong
- Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands; and
| | - Arthur J A T Braat
- Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands; and
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Gorji L, Aoun H, Critchfield J, Al Hallak N, Beal EW. Locoregional Therapy for Intrahepatic Cholangiocarcinoma: The Role of Intra-Arterial Therapies. Cancers (Basel) 2023; 15:4727. [PMID: 37835420 PMCID: PMC10571998 DOI: 10.3390/cancers15194727] [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: 09/03/2023] [Revised: 09/18/2023] [Accepted: 09/22/2023] [Indexed: 10/15/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is a rare disease with a rising incidence. While surgical resection is the only curative option, the disease process is often identified in advanced stages, as this malignancy often remains clinically silent in early development. Only one-third of patients are eligible for resection at the time of diagnosis. For patients who cannot undergo resection, intra-arterial therapies are reasonable palliative treatment options; in rare occasions, these may be bridging therapies, as well. The premise of bland embolization and most chemoembolization intra-arterial therapies is that the arterial supply of the tumor is occluded to induce tumor necrosis, while radioembolization utilizes the arterial flow of the tumor to deliver radiation therapy. In this review, we discuss the use of transarterial embolization, transarterial chemoembolization, and selective internal radiation therapy for the treatment of ICC. Phase III randomized controlled clinical trials are difficult to tailor to this extremely rare and aggressive disease, but ultimately, further investigation should be pursued to define the patient population that will derive the greatest benefit from each modality.
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Affiliation(s)
- Leva Gorji
- Department of Surgery, Kettering Health, Dayton, OH 45402, USA;
| | - Hussein Aoun
- Department of Interventional Radiology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA; (H.A.); (J.C.)
| | - Jeffrey Critchfield
- Department of Interventional Radiology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA; (H.A.); (J.C.)
| | - Najeeb Al Hallak
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA;
| | - Eliza W. Beal
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA;
- Department of Surgery, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA
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Hosseini Shabanan S, Nezami N, Abdelsalam ME, Sheth RA, Odisio BC, Mahvash A, Habibollahi P. Selective Internal Radiation Therapy with Yttrium-90 for Intrahepatic Cholangiocarcinoma: A Systematic Review on Post-Treatment Dosimetry and Concomitant Chemotherapy. Curr Oncol 2022; 29:3825-3848. [PMID: 35735415 PMCID: PMC9222092 DOI: 10.3390/curroncol29060306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 05/18/2022] [Accepted: 05/23/2022] [Indexed: 01/27/2023] Open
Abstract
Selective internal radiation therapy (SIRT) with yttrium-90 (90Y)-loaded microspheres is increasingly used for the treatment of Intrahepatic Cholangiocarcinoma (ICC). Dosimetry verifications post-treatment are required for a valid assessment of any dose-response relationship. We performed a systematic review of the literature to determine how often clinics conducted post-treatment dosimetry verification to measure the actual radiation doses delivered to the tumor and to the normal liver in patients who underwent SIRT for ICC, and also to explore the corresponding dose-response relationship. We also investigated other factors that potentially affect treatment outcomes, including the type of microspheres used and concomitant chemotherapy. Out of the final 47 studies that entered our study, only four papers included post-treatment dosimetry studies after SIRT to quantitatively assess the radiation doses delivered. No study showed that one microsphere type provided a benefit over another, one study demonstrated better imaging-based response rates associated with the use of glass-based TheraSpheres, and two studies found similar toxicity profiles for different types of microspheres. Gemcitabine and cisplatin were the most common chemotherapeutic drugs for concomitant administration with SIRT. Future studies of SIRT for ICC should include dosimetry to optimize treatment planning and post-treatment radiation dosage measurements in order to reliably predict patient responses and liver toxicity.
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Affiliation(s)
| | - Nariman Nezami
- Division of Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA;
- Experimental Therapeutics Program, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USA
| | - Mohamed E. Abdelsalam
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (M.E.A.); (R.A.S.); (B.C.O.); (A.M.)
| | - Rahul Anil Sheth
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (M.E.A.); (R.A.S.); (B.C.O.); (A.M.)
| | - Bruno C. Odisio
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (M.E.A.); (R.A.S.); (B.C.O.); (A.M.)
| | - Armeen Mahvash
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (M.E.A.); (R.A.S.); (B.C.O.); (A.M.)
| | - Peiman Habibollahi
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (M.E.A.); (R.A.S.); (B.C.O.); (A.M.)
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Nuclear Medicine Therapy in primary liver cancers. Nucl Med Mol Imaging 2022. [DOI: 10.1016/b978-0-12-822960-6.00180-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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Fabritius MP, Ben Khaled N, Kunz WG, Ricke J, Seidensticker M. Image-Guided Local Treatment for Unresectable Intrahepatic Cholangiocarcinoma-Role of Interventional Radiology. J Clin Med 2021; 10:jcm10235574. [PMID: 34884275 PMCID: PMC8658286 DOI: 10.3390/jcm10235574] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 11/24/2021] [Accepted: 11/24/2021] [Indexed: 01/27/2023] Open
Abstract
Intrahepatic cholangiocarcinoma is a highly aggressive malignancy with an increasing incidence in recent years. Prognosis is poor and most patients are not eligible for resection at the time of initial diagnosis due to the anatomic location, inadequate hepatic reserve, limiting comorbidities or metastatic disease. Several locoregional therapies from the field of interventional radiology exist for patients who are not amenable for surgery, or in case of local recurrence as a single treatment modality or combined with systemic treatment. To date, evidence is limited, with most conclusions drawn from single-center studies with small patient cohorts, often treated in the salvage situation or for local recurrence after initial resection. Nevertheless, the results are promising and suggest a survival benefit in selected patients. This narrative review focuses on the use of different locoregional treatment options for intrahepatic cholangiocarcinoma.
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Affiliation(s)
- Matthias P. Fabritius
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany; (W.G.K.); (J.R.)
- Correspondence: (M.P.F); (M.S.)
| | - Najib Ben Khaled
- Department of Medicine II, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany;
- German Cancer Consortium (DKTK), Partner Site Munich, Marchioninistr. 15, 81377 Munich, Germany
| | - Wolfgang G. Kunz
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany; (W.G.K.); (J.R.)
| | - Jens Ricke
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany; (W.G.K.); (J.R.)
| | - Max Seidensticker
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany; (W.G.K.); (J.R.)
- Correspondence: (M.P.F); (M.S.)
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Assessment of radiation sensitivity of unresectable intrahepatic cholangiocarcinoma in a series of patients submitted to radioembolization with yttrium-90 resin microspheres. Sci Rep 2021; 11:19745. [PMID: 34611210 PMCID: PMC8492793 DOI: 10.1038/s41598-021-99219-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 08/25/2021] [Indexed: 01/23/2023] Open
Abstract
Radioembolization is a valuable therapeutic option in patients with unresectable intrahepatic cholangiocarcinoma. The essential implementation of the absorbed dose calculation methods should take into account also the specific tumor radiosensitivity, expressed by the α parameter. Purpose of this study was to retrospectively calculate it in a series of patients with unresectable intrahepatic cholangiocarcinoma submitted to radioembolization. Twenty-one therapeutic procedures in 15 patients were analysed. Tumor absorbed doses were calculated processing the post-therapeutic 90Y-PET/CT images and the pre-treatment contrast-enhanced CT scans. Tumor absorbed dose and pre- and post-treatment tumor volumes were used to calculate α and α3D parameters (dividing targeted liver in n voxels of the same volume with specific voxel absorbed dose). A tumor volume reduction was observed after treatment. The median of tumor average absorbed dose was 93 Gy (95% CI 81–119) and its correlation with the residual tumor mass was statistically significant. The median of α and α3D parameters was 0.005 Gy−1 (95% CI 0.004–0.008) and 0.007 Gy−1 (95% CI 0.005–0.015), respectively. Multivariate analysis showed tumor volume and tumor absorbed dose as significant predictors of the time to tumor progression. The knowledge of radiobiological parameters gives the possibility to decide the administered activity in order to improve the outcome of the treatment.
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Yu Q, Liu C, Pillai A, Ahmed O. Twenty Years of Radiation Therapy of Unresectable Intrahepatic Cholangiocarinoma: Internal or External? A Systematic Review and Meta-Analysis. Liver Cancer 2021; 10:433-450. [PMID: 34721506 PMCID: PMC8527917 DOI: 10.1159/000516880] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Accepted: 04/25/2021] [Indexed: 02/04/2023] Open
Abstract
PURPOSE Both external beam radiation therapy (EBRT) and selective-internal radiation therapy (SIRT) are implemented to treat unresectable intrahepatic cholangiocarcinoma (iCCA). The present study aimed to evaluate the efficacy of EBRT and SIRT in managing iCCA through a systematic review and meta-analysis. METHODS PubMed and Cochrane database were queried to search for studies published from January 2000 toJune 2020 without language restrictions. Median survival time, overall survival, and radiological response were extracted. Secondary outcomes such as complication rates, predictors of survival, and downstage to surgery were pooled. Patient-level survival data were obtained to generate Kaplan-Meier survival graph. Pooled outcomes were analyzed with a random-effect model. RESULTS Twenty-nine and 20 studies including 732 and 443 patients from the SIRT and EBRT groups were included in the present study. From initial radiation treatment, the median survival time for patients who underwent SIRT and EBRT were 12.0 (95% confidence interval [CI]: 10.8-14.6) and 13.6 (95% CI: 11.1-16.0) months, respectively. As first-line therapy, the median survival time was 36.1 (95% CI: 20.6-39.5) months for SIRT and 11.0 (95% CI: 9.3-13.6) months for EBRT. Both radiation modalities were effective in downstaging initially unresectable iCCA to surgery (SIRT: 30.5%; EBRT: 18.3%). Patients in the SIRT group encountered more post-embolization abdominal pain (6.9 vs. 2.2%), ulcer (1.0 vs. 0.5%), nausea (1.6 vs. 0.7%), anorexia (5.9 vs. 0%), thrombocytopenia (7.3 vs. 6.0%), hyperbilirubinemia (5.2 vs. 2.1%), and hypoalbuminemia (13.2 vs. 3.3%), whereas EBRT was associated with higher rates of anemia (0.6 vs. 7.5%) and neutropenia (6.5 vs. 11.0%). CONCLUSIONS Both EBRT and SIRT were safe and effective in treating unresectable iCCA. However, available evidence was highly heterogeneous regarding patient population, limiting fair comparison between 2 radiation modalities. Future high-quality comparative studies are warranted.
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Affiliation(s)
- Qian Yu
- Department of Surgery, Cleveland Clinic Florida, Weston, Florida, USA,*Qian Yu, yuqian1006*gmail.com
| | - Chenyu Liu
- Ben May Department of Cancer Research, University of Chicago, Chicago, Illinois, USA
| | - Anjana Pillai
- Division of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, Illinois, USA
| | - Osman Ahmed
- Division of Interventional Radiology, Department of Radiology, University of Chicago, Chicago, Illinois, USA
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Mosconi C, Solaini L, Vara G, Brandi N, Cappelli A, Modestino F, Cucchetti A, Golfieri R. Transarterial Chemoembolization and Radioembolization for Unresectable Intrahepatic Cholangiocarcinoma-a Systemic Review and Meta-Analysis. Cardiovasc Intervent Radiol 2021; 44:728-738. [PMID: 33709272 DOI: 10.1007/s00270-021-02800-w] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Accepted: 02/05/2021] [Indexed: 01/07/2023]
Abstract
PURPOSE Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis, when unresectable; therefore, intra-arterial therapies (IAT) such as trans-arterial chemoembolization (TACE) and trans-arterial radioembolization (TARE) have been employed. With the present systematic review and meta-analysis, we aimed to analyse published studies to understand if one IAT can be superior to the alternative. MATERIALS AND METHODS A systematic search of PubMed and Web of Science databases was performed for articles published until 1 March 2020 relevant to IAT for ICC. Overall survival was the primary end point. Occurrence of clinical adverse events and tumour overall response were secondary outcome measures. RESULTS A total of 31 articles (of 793, n.1695 patients) were selected for data extraction, 13 were on TACE (906 patients) and 18 were on TARE (789 patients). Clinical and tumour characteristics showed moderate heterogeneity between the two groups. The median survival after TACE was 14.2 months while after TARE was 13.5 months (95%C.I.: 11.4-16.1). The survival difference was small (d = 0.112) at 1 year and negligible at 2 years (d = 0.028) and at 3 years (d = 0.049). The radiological objective response after TACE was 20.6% and after TARE was 19.3% (d = 0.032). Clinical adverse events occurred in 58.5% after TACE, more frequently than after TARE (43.0%, d = 0.314). CONCLUSION In conclusion, IATs are promising treatments for improving outcomes for patients with unresectable ICC. To date, TACE and TARE provide similar good outcomes, except for adverse events. Therefore, the decision about techniques is determined by ability to utilize these resources and patient specific factors (liver function or lesion dimension).
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Affiliation(s)
- Cristina Mosconi
- Department of Radiology, IRCCS, Azienda Ospedaliero-Universitaria Di Bologna, Sant'Orsola-Malpighi Hospital, Via Albertoni 15, 40138, Bologna, Italy.
| | - Leonardo Solaini
- Department of Medical and Surgical Sciences-DIMEC, Alma Mater Studiorum - University of Bologna, Bologna, Italy
- Department of Surgery, Morgagni - Pierantoni Hospital, Forlì, Italy
| | - Giulio Vara
- Department of Radiology, IRCCS, Azienda Ospedaliero-Universitaria Di Bologna, Sant'Orsola-Malpighi Hospital, Via Albertoni 15, 40138, Bologna, Italy
| | - Nicolò Brandi
- Department of Radiology, IRCCS, Azienda Ospedaliero-Universitaria Di Bologna, Sant'Orsola-Malpighi Hospital, Via Albertoni 15, 40138, Bologna, Italy
| | - Alberta Cappelli
- Department of Radiology, IRCCS, Azienda Ospedaliero-Universitaria Di Bologna, Sant'Orsola-Malpighi Hospital, Via Albertoni 15, 40138, Bologna, Italy
| | - Francesco Modestino
- Department of Radiology, IRCCS, Azienda Ospedaliero-Universitaria Di Bologna, Sant'Orsola-Malpighi Hospital, Via Albertoni 15, 40138, Bologna, Italy
| | - Alessandro Cucchetti
- Department of Medical and Surgical Sciences-DIMEC, Alma Mater Studiorum - University of Bologna, Bologna, Italy
- Department of Surgery, Morgagni - Pierantoni Hospital, Forlì, Italy
| | - Rita Golfieri
- Department of Radiology, IRCCS, Azienda Ospedaliero-Universitaria Di Bologna, Sant'Orsola-Malpighi Hospital, Via Albertoni 15, 40138, Bologna, Italy
- Department of Specialized, Diagnostic and Experimental Medicine - DIMES, Alma Mater Studiorum - University of Bologna, Bologna, Italy
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Gerke O, Ehlers K, Motschall E, Høilund-Carlsen PF, Vach W. PET/CT-Based Response Evaluation in Cancer-a Systematic Review of Design Issues. Mol Imaging Biol 2021; 22:33-46. [PMID: 31016638 DOI: 10.1007/s11307-019-01351-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Positron emission tomography/x-ray computed tomography (PET/CT) has long been discussed as a promising modality for response evaluation in cancer. When designing respective clinical trials, several design issues have to be addressed, especially the number/timing of PET/CT scans, the approach for quantifying metabolic activity, and the final translation of measurements into a rule. It is unclear how well these issues have been tackled in quest of an optimised use of PET/CT in response evaluation. Medline via Ovid and Science Citation Index via Web of Science were systematically searched for articles from 2015 on cancer patients scanned with PET/CT before and during/after treatment. Reports were categorised as being either developmental or evaluative, i.e. focusing on either the establishment or the evaluation of a rule discriminating responders from non-responders. Of 124 included papers, 112 (90 %) were accuracy and/or prognostic studies; the remainder were response-curve studies. No randomised controlled trials were found. Most studies were prospective (62 %) and from single centres (85 %); median number of patients was 38.5 (range 5-354). Most (69 %) of the studies employed only one post-baseline scan. Quantification was mainly based on SUVmax (91 %), while change over time was most frequently used to combine measurements into a rule (79 %). Half of the reports were categorised as developmental, the other half evaluative. Most development studies assessed only one element (35/62, 56 %), most frequently the choice of cut-off points (25/62, 40 %). In summary, the majority of studies did not address the essential open issues in establishing PET/CT for response evaluation. Reasonably sized multicentre studies are needed to systematically compare the many different options when using PET/CT for response evaluation.
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Affiliation(s)
- Oke Gerke
- Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark. .,Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
| | - Karen Ehlers
- Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark.,Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Edith Motschall
- Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
| | - Poul Flemming Høilund-Carlsen
- Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark.,Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Werner Vach
- Department of Orthopaedics and Traumatology, University Hospital Basel, Basel, Switzerland
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Bozkurt M, Eldem G, Bozbulut UB, Bozkurt MF, Kılıçkap S, Peynircioğlu B, Çil B, Lay Ergün E, Volkan-Salanci B. Factors affecting the response to Y-90 microsphere therapy in the cholangiocarcinoma patients. Radiol Med 2020; 126:323-333. [PMID: 32594427 DOI: 10.1007/s11547-020-01240-9] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2020] [Accepted: 06/07/2020] [Indexed: 01/08/2023]
Abstract
OBJECTIVE The aim of this study was to assess the early therapy response in patients with unresectable CCA who received Y-90 microsphere therapy for CCA and define the factors related to therapy response. MATERIALS AND METHODS Data of 19 patients [extrahepatic (n: 6) and intrahepatic (n: 13)] who received 24 sessions of Y-90 microsphere therapy [glass (n: 13) and resin (n: 11)] were retrospectively evaluated. Tumor load, tumor size, therapy response evaluation by RECIST1.1 criteria (n: 13), tumor lesion glycolysis (TLG), metabolic tumor volume (MTV), and metabolic therapy responses were evaluated (n: 8) using PERCIST1.0 criteria. RESULTS No significant relation was found between therapy response and tumor localization, treated liver lobe, type of Y90 microspheres, the presence of previous therapies, perfusion pattern on hepatic artery perfusion scintigraphy, or patient demographics. The mean overall survival (OS) was 11.9 ± 2.3 months and was similar after both resin and glass Y90 microspheres; however, it was longer RECIST responders (p: 0.005). MTV and TLG values significantly decreased after therapy, and ΔMTV (- 45.4% ± 12.1) was found to be positively correlated with OS. No statistical difference was found between iCCA and eCCA, in terms of OS and response to therapy. Although not quantitatively displayed, better-perfused areas on HAPS images had a better metabolic response and less perfused areas were prone to local recurrences. CONCLUSIONS Both resin and glass microsphere therapy can be applied safely to iCCA and eCCA patients. Early therapy response can be evaluated with both RECIST and PERCIST criteria. Both anatomical and metabolic therapy response evaluations give complementary information.
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Affiliation(s)
- Mehmet Bozkurt
- Department of Nuclear Medicine, Bakirkoy Dr.Sadi Konuk Training and Research Hospital, Istanbul, Turkey
| | - Gonca Eldem
- Department of Radiology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | | | - Murat Fani Bozkurt
- Department of Nuclear Medicine, Faculty of Medicine, Hacettepe University, 06100, Sıhhiye, Ankara, Turkey
| | - Saadettin Kılıçkap
- Department of Medical Oncology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Bora Peynircioğlu
- Department of Radiology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Barbaros Çil
- Department of Radiology, Koç University, Istanbul, Turkey
| | - Eser Lay Ergün
- Department of Nuclear Medicine, Faculty of Medicine, Hacettepe University, 06100, Sıhhiye, Ankara, Turkey
| | - Bilge Volkan-Salanci
- Department of Nuclear Medicine, Faculty of Medicine, Hacettepe University, 06100, Sıhhiye, Ankara, Turkey.
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12
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Edeline J, Touchefeu Y, Guiu B, Farge O, Tougeron D, Baumgaertner I, Ayav A, Campillo-Gimenez B, Beuzit L, Pracht M, Lièvre A, Le Sourd S, Boudjema K, Rolland Y, Boucher E, Garin E. Radioembolization Plus Chemotherapy for First-line Treatment of Locally Advanced Intrahepatic Cholangiocarcinoma: A Phase 2 Clinical Trial. JAMA Oncol 2020; 6:51-59. [PMID: 31670746 PMCID: PMC6824230 DOI: 10.1001/jamaoncol.2019.3702] [Citation(s) in RCA: 187] [Impact Index Per Article: 37.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Accepted: 07/02/2019] [Indexed: 12/29/2022]
Abstract
IMPORTANCE Patients with unresectable intrahepatic cholangiocarcinoma (ICC) have a poor prognosis. Selective internal radiotherapy (SIRT) is a promising treatment option for hepatic tumors, but no prospective studies of combination SIRT with chemotherapy have been published to our knowledge. OBJECTIVE To determine the response rate after SIRT combined with chemotherapy in patients with unresectable ICC. DESIGN, SETTING, AND PARTICIPANTS This phase 2 clinical trial, the Yttrium-90 Microspheres in Cholangiocarcinoma (MISPHEC) trial, included patients with unresectable ICC who have never received chemotherapy or intra-arterial therapy and were treated at 7 centers which had experience with SIRT between November 12, 2013, and June 21, 2016. Statistical analysis was performed from March 31, 2017, to June 17, 2019. INTERVENTIONS Concomitant first-line chemotherapy with cisplatin, 25 mg/m2, and gemcitabine, 1000 mg/m2 (gemcitabine reduced to 300 mg/m2 for the cycles just before and after SIRT), on days 1 and 8 of a 21-day cycle for 8 cycles. Selective internal radiotherapy was administered during cycle 1 (1 hemiliver disease) or cycles 1 and 3 (disease involving both hemilivers) using glass Y90 microspheres. MAIN OUTCOMES AND MEASURES Response rate at 3 months according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Secondary end points were toxic effects, progression-free survival, overall survival, disease control rate, and response rate according to Choi criteria. RESULTS Of 41 patients included in the study, 26 (63%) were male, with a mean (SD) age of 64.0 (10.7) years. Response rate according to RECIST was 39% (90% CI, 26%-53%) at 3 months according to local review and was confirmed at 41% as best response by central review; disease control rate was 98%. According to Choi criteria, the response rate was 93%. After a median follow-up of 36 months (95% CI, 26-52 months), median progression-free survival was 14 months (95% CI, 8-17 months), with progression-free survival rates of 55% at 12 months and 30% at 24 months. Median overall survival was 22 months (95% CI, 14-52 months), with overall survival rates of 75% at 12 months and 45% at 24 months. Of 41 patients, 29 (71%) had grades 3 to 4 toxic effects; 9 patients (22%) could be downstaged to surgical intervention, with 8 (20%) achieving R0 (microscopic-free margins) surgical resection. After a median of 46 months (95% CI, 31 months to not reached) after surgery, median relapse-free survival was not reached among patients who underwent resection. CONCLUSIONS AND RELEVANCE Combination chemotherapy and SIRT had antitumor activity as first-line treatment of unresectable ICC, and a significant proportion of patients were downstaged to surgical intervention. A phase 3 trial is ongoing.
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Affiliation(s)
- Julien Edeline
- Department of Medical Oncology, Centre Eugène Marquis, Rennes, France
- Université Rennes, IndianaSERM, IndianaRA, Centre de Lutte contre le Cancer Eugène Marquis, Institut NUMECAN (Nutrition Metabolisms and Cancer), Rennes, France
| | | | - Boris Guiu
- Centre Hospitalier Universitaire Montpellier, Montpellier, France
| | - Olivier Farge
- Centre Hospitalier Universitaire Beaujon, Clichy, France
| | - David Tougeron
- Centre Hospitalier Universitaire Poitiers, Poitiers, France
| | | | - Ahmet Ayav
- Centre Hospitalier Universitaire Nancy, Nancy, France
| | - Boris Campillo-Gimenez
- Department of Medical Oncology, Centre Eugène Marquis, Rennes, France
- INSERM, LTSI U1099, Université Rennes 1, Rennes, France
| | - Luc Beuzit
- Radiology, Centre Hospitalier Universitaire Pontchaillou, Rennes, France
| | - Marc Pracht
- Department of Medical Oncology, Centre Eugène Marquis, Rennes, France
| | - Astrid Lièvre
- Gastroenterology, Centre Hospitalier Universitaire Pontchaillou, Rennes, France
- Univ Rennes, Inserm, Regional Cancer Center Eugène Marquis, Chemistry Oncogenesis Stress Signaling-UMR1242, Rennes, France
| | - Samuel Le Sourd
- Department of Medical Oncology, Centre Eugène Marquis, Rennes, France
| | - Karim Boudjema
- Hepatobiliary Surgery, Centre Hospitalier Universitaire Pontchaillou, Rennes, France
| | - Yan Rolland
- Radiology, Centre Eugène Marquis, Rennes, France
| | - Eveline Boucher
- Department of Medical Oncology, Centre Eugène Marquis, Rennes, France
| | - Etienne Garin
- Nuclear Medicine, Centre Eugène Marquis, Rennes, France
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13
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Upregulation of DPY30 promotes cell proliferation and predicts a poor prognosis in cholangiocarcinoma. Biomed Pharmacother 2019; 123:109766. [PMID: 31846841 DOI: 10.1016/j.biopha.2019.109766] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Revised: 11/23/2019] [Accepted: 12/04/2019] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVES Modification of lysine 4 on histone H3 methylation by SET1 and MLL family methyltransferase complexes is tightly linked to cancer progression. DPY30 is an important subunit of SET1 and MLL complexes, however, its expression and roles in cancer progression was little known, especially in cholangiocarcinoma (CCA). MATERIALS AND METHODS The Q-PCR and IHC were performed to detect the levels of DPY30 mRNA and protein in CCA tissues. Effect of DPY30 knockdown on the proliferation of CCA cells was detected by MTS and colony formation, and cell cycle distribution was analyzed by flow cytometer. The glucose uptake, lactate release and ATP production assays were performed to detect the glycolysis of CCA cells. RESULTS The level of DPY30 mRNA and protein in CCA tissues were all significantly higher than that of pericancer tissues, and its upregulation was closely associated with pathological differentiation, tumor size, and TNM stage. In addition, Kaplan-Meier analysis of overall survival revealed that DPY30 upregulation was significantly associated with poor survival, and univariate and multivariate analysis indicated that it was an independently prognosis factor in CCA patients. Moreover, DPY30 knockdown inhibited in-vitro growth and induced cell cycle arrest at G2/M and decreased glycolysis in CCA cells. CONCLUSIONS DPY30 upregulation may promote the development of CCA and was associated with the aggressive malignant behavior and poor survival outcome of CCA patients. DPY30 might serve as a potential novel target for treatment of CCA patients.
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Zhen Y, Liu B, Chang Z, Ren H, Liu Z, Zheng J. A pooled analysis of transarterial radioembolization with yttrium-90 microspheres for the treatment of unresectable intrahepatic cholangiocarcinoma. Onco Targets Ther 2019; 12:4489-4498. [PMID: 31239717 PMCID: PMC6560193 DOI: 10.2147/ott.s202875] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Accepted: 04/15/2019] [Indexed: 12/16/2022] Open
Abstract
Purpose: The aim of this pooled analysis was to evaluate the clinical efficacy and safety of transarterial radioembolization (TARE) with yttrium-90 (90Y) microspheres for the treatment of unresectable intrahepatic cholangiocarcinoma (ICC). Methods: We searched the Cochrane Library, Embase, PubMed, SCI with the English language from inception to October 2018. A pooled analysis was conducted using Stata software. Results: There were 16 eligible studies included in this pooled analysis. The pooled median overall survival (OS) from 12 studies was 14.3 (95% CI: 11.9-17.1) months. Based on Response Evaluation Criteria in Solid Tumors (RECIST), no complete response was reported, and the median of partial response, stable disease and progressive disease were 11.5% (range: 4.8-35.3%), 61.5% (range: 42.9-81.3%) and 22.7% (range: 12.5-52.4%) respectively. The pooled disease control rate (DCR) from nine studies was 77.2% (95% CI: 70.2-84.2%). According to the type of microspheres, subgroup analysis was performed, the median OS in the glass microspheres group was 14.0 (95% CI: 9.1-21.4) months, and 14.3 (95% CI: 11.5-17.8) months in the resin microspheres group. The DCR was 77.3% (95% CI: 63.5-91.1%) and 77.4% (95% CI: 66.8-87.9%) in the glass and resin microspheres groups respectively. Most of the side effects reported in the included studies were mild and did not require intervention. Conclusion: TARE with 90Y microspheres is safe and effective for patients with unresectable ICC with acceptable side effects. And it seems that the type of microsphere has no influence on therapeutic efficacy.
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Affiliation(s)
- Yanhua Zhen
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China
| | - Bin Liu
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China
| | - Zhihui Chang
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China
| | - Haiyan Ren
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China
| | - Zhaoyu Liu
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China
| | - Jiahe Zheng
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China
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15
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Bourien H, Palard X, Rolland Y, Le Du F, Beuzit L, Uguen T, Le Sourd S, Pracht M, Manceau V, Lièvre A, Boudjema K, Garin E, Edeline J. Yttrium-90 glass microspheres radioembolization (RE) for biliary tract cancer: a large single-center experience. Eur J Nucl Med Mol Imaging 2018; 46:669-676. [DOI: 10.1007/s00259-018-4199-5] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Accepted: 10/17/2018] [Indexed: 01/27/2023]
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16
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Decrease in total lesion glycolysis and survival after yttrium-90-radioembolization in poorly differentiated hepatocellular carcinoma with portal vein tumour thrombosis. Nucl Med Commun 2018; 39:845-852. [DOI: 10.1097/mnm.0000000000000879] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
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17
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Gangi A, Shah J, Hatfield N, Smith J, Sweeney J, Choi J, El-Haddad G, Biebel B, Parikh N, Arslan B, Hoffe SE, Frakes JM, Springett GM, Anaya DA, Malafa M, Chen DT, Chen Y, Kim RD, Shridhar R, Kis B. Intrahepatic Cholangiocarcinoma Treated with Transarterial Yttrium-90 Glass Microsphere Radioembolization: Results of a Single Institution Retrospective Study. J Vasc Interv Radiol 2018; 29:1101-1108. [PMID: 30042074 DOI: 10.1016/j.jvir.2018.04.001] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Revised: 03/25/2018] [Accepted: 04/01/2018] [Indexed: 12/14/2022] Open
Abstract
PURPOSE To evaluate the efficacy and safety of transarterial yttrium-90 glass microsphere radioembolization in patients with unresectable intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS Retrospective review of 85 consecutive patients (41 men and 44 women; age, 73.4 ± 9.3 years) was performed. Survival data were analyzed by the Kaplan-Meier method, Cox regression models, and the log-rank test. RESULTS Median overall survival (OS) from diagnosis was 21.4 months (95% confidence interval [CI]: 16.6-28.4); median OS from radioembolization was 12.0 months (95% CI: 8.0-15.2). Seven episodes of severe toxicity occurred. At 3 months, 6.2% of patients had partial response, 64.2% had stable disease, and 29.6% had progressive disease. Median OS from radioembolization was significantly longer in patients with Eastern Cooperative Oncology Group (ECOG) scores of 0 and 1 than patients with an ECOG score of 2 (18.5 vs 5.5 months, P = .0012), and median OS from radioembolization was significantly longer in patients with well-differentiated histology than patients with poorly differentiated histology (18.6 vs 9.7 months, P = .012). Patients with solitary tumors had significantly longer median OS from radioembolization than patients with multifocal disease (25 vs. 6.1 months, P = .006). The absence of extrahepatic metastasis was associated with significantly increased median OS (15.2 vs. 6.8 months, P = .003). Increased time from diagnosis to radioembolization was a negative predictor of OS. The morphology of the tumor (mass-forming or infiltrative, hyper- or hypo-enhancing) had no effect on survival. Post-treatment increased cancer antigen 19-9 level, increased international normalized ratio, decreased albumin, increased bilirubin, increased aspartate aminotransferase, and increased Model for End-Stage Liver Disease score were significant predictors of decreased OS. CONCLUSIONS These data support the therapeutic role of radioembolization for the treatment of unresectable ICC with good efficacy and an acceptable safety profile.
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Affiliation(s)
- Alexandra Gangi
- Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612; Department of Surgery, Cedars Sinai Medical Center, Los Angeles, California
| | - Jehan Shah
- Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612
| | - Nathan Hatfield
- Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612
| | - Johnna Smith
- Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612
| | - Jennifer Sweeney
- Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612
| | - Junsung Choi
- Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612
| | - Ghassan El-Haddad
- Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612
| | - Benjamin Biebel
- Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612
| | - Nainesh Parikh
- Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612
| | - Bulent Arslan
- Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612; Vascular and Interventional Radiology, Rush University Medical Center, Chicago, Illinois
| | - Sarah E Hoffe
- Radiation Oncology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612
| | - Jessica M Frakes
- Radiation Oncology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612
| | - Gregory M Springett
- Gastrointestinal Oncology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612
| | - Daniel A Anaya
- Gastrointestinal Oncology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612
| | - Mokenge Malafa
- Gastrointestinal Oncology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612
| | - Dung-Tsa Chen
- Biostatistics and Bioinformatics, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612
| | - Yunyun Chen
- Biostatistics and Bioinformatics, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612
| | - Richard D Kim
- Gastrointestinal Oncology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612
| | - Ravi Shridhar
- Radiation Oncology, Florida Hospital Orlando, Orlando, Florida
| | - Bela Kis
- Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612.
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18
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Kis B, El-Haddad G, Sheth RA, Parikh NS, Ganguli S, Shyn PB, Choi J, Brown KT. Liver-Directed Therapies for Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma. Cancer Control 2018; 24:1073274817729244. [PMID: 28975829 PMCID: PMC5937250 DOI: 10.1177/1073274817729244] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHC) are primary liver cancers where all or most of the tumor burden is usually confined to the liver. Therefore, locoregional liver-directed therapies can provide an opportunity to control intrahepatic disease with minimal systemic side effects. The English medical literature and clinical trials were reviewed to provide a synopsis on the available liver-directed percutaneous therapies for HCC and IHC. Locoregional liver-directed therapies provide survival benefit for patients with HCC and IHC compared to best medical treatment and have lower comorbid risks compared to surgical resection. These treatment options should be considered, especially in patients with unresectable disease.
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Affiliation(s)
- Bela Kis
- 1 Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Ghassan El-Haddad
- 1 Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Rahul A Sheth
- 2 Department of Interventional Radiology, MD Anderson Cancer Center, Houston, TX, USA
| | - Nainesh S Parikh
- 1 Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Suvranu Ganguli
- 3 Center for Image Guided Cancer Therapy, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Paul B Shyn
- 4 Department of Radiology, Abdominal Imaging and Intervention, Brigham and Women's, Boston, MA, USA
| | - Junsung Choi
- 1 Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Karen T Brown
- 5 Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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19
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Filippi L, Schillaci O, Cianni R, Bagni O. Yttrium-90 resin microspheres and their use in the treatment of intrahepatic cholangiocarcinoma. Future Oncol 2018; 14:809-818. [DOI: 10.2217/fon-2017-0443] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is a severe and rapidly progressive hepatic tumor. Surgery is often impracticable due to locally advanced presentation. On the other hand, chemotherapy has demonstrated only limited effectiveness. For these reasons, liver-directed therapies have been successfully applied for treating ICC. In particular, radioembolization with Yttrium-90 (90Y)-labeled spheres has been reported to be a promising therapeutic approach for this neoplasia. Two commercial forms of 90Y-labeled spheres are available: glass (TheraSphere®) and resin (SIR-Spheres®) microspheres. The aim of the present paper is to review the existing literature on the use of the resin microspheres for the treatment of unresectable and chemorefractory ICC, focusing on the methodology, clinical applications and side effects.
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Affiliation(s)
- Luca Filippi
- Nuclear Medicine Unit, “Santa Maria Goretti” Hospital, Latina, Italy
| | - Orazio Schillaci
- Department of Biomedicine & Prevention, University Tor Vergata, Rome, Italy; IRCCS Neuromed, Pozzilli, Italy
| | - Roberto Cianni
- Interventional Radiology Unit, “San Camillo Hospital”, Rome, Italy
| | - Oreste Bagni
- Nuclear Medicine Unit, “Santa Maria Goretti” Hospital, Latina, Italy
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20
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Aarntzen EH, Heijmen L, Oyen WJ. 18F-FDG PET/CT in Local Ablative Therapies: A Systematic Review. J Nucl Med 2018; 59:551-556. [DOI: 10.2967/jnumed.117.198184] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2017] [Accepted: 12/13/2017] [Indexed: 12/13/2022] Open
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21
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Reimer P, Virarkar MK, Binnenhei M, Justinger M, Schön MR, Tatsch K. Prognostic Factors in Overall Survival of Patients with Unresectable Intrahepatic Cholangiocarcinoma Treated by Means of Yttrium-90 Radioembolization: Results in Therapy-Naïve Patients. Cardiovasc Intervent Radiol 2018; 41:744-752. [DOI: 10.1007/s00270-017-1871-2] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2017] [Accepted: 12/29/2017] [Indexed: 12/18/2022]
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22
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Kennedy A, Brown DB, Feilchenfeldt J, Marshall J, Wasan H, Fakih M, Gibbs P, Knuth A, Sangro B, Soulen MC, Pittari G, Sharma RA. Safety of selective internal radiation therapy (SIRT) with yttrium-90 microspheres combined with systemic anticancer agents: expert consensus. J Gastrointest Oncol 2017; 8:1079-1099. [PMID: 29299370 PMCID: PMC5750172 DOI: 10.21037/jgo.2017.09.10] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Accepted: 09/20/2017] [Indexed: 12/12/2022] Open
Abstract
Selective internal radiation therapy (SIRT) with microspheres labelled with the β-emitter yttrium-90 (Y-90) enables targeted delivery of radiation to hepatic tumors. SIRT is primarily used to treat inoperable primary or metastatic liver tumors. Eligible patients have usually been exposed to a variety of systemic anticancer therapies, including cytotoxic agents, targeted biologics, immunotherapy and peptide receptor radionuclide therapy (PRRT). All these treatments have potential interactions with SIRT; however, robust evidence on the safety of these potential combinations is lacking. This paper provides current clinical experiences and expert consensus guidelines for the use of SIRT in combination with the anticancer treatment agents likely to be encountered in clinical practice. It was agreed by the expert panel that precautions need to be taken with certain drugs, but that, in general, systemic therapies do not necessarily have to be stopped to perform SIRT. The authors recommend stopping vascular endothelial growth factor inhibitors 4-6 weeks before SIRT, and restart after the patient has recovered from the procedure. It may also be prudent to stop potent radiosensitizers such as gemcitabine therapy 4 weeks before SIRT, and restart treatment at least 2‒4 weeks later. Data from phase III studies combining SIRT with fluorouracil (5FU) or folinic acid/5FU/oxaliplatin (FOLFOX) suggest that hematological toxicity is more common from the combination than it is from chemotherapy without SIRT. There is no evidence to suggest that chemotherapy increases SIRT-specific gastro-intestinal or liver toxicities.
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Affiliation(s)
- Andrew Kennedy
- Radiation Oncology Research, Sarah Cannon Research Institute, Nashville, Tennessee, USA
| | - Daniel B. Brown
- Department of Radiology and Radiologic Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | | | - John Marshall
- Hematology and Oncology Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC, USA
| | - Harpreet Wasan
- Imperial College, Division of Cancer, Hammersmith Hospital, London, UK
| | - Marwan Fakih
- Department of Medical Oncology & Therapeutics Research, City of Hope, Duarte, California, USA
| | - Peter Gibbs
- Western Hospital, Footscray, Victoria, Australia
| | - Alexander Knuth
- National Center for Cancer Care and Research, HMC, Doha, Qatar
| | - Bruno Sangro
- Liver Unit, Clinica Universidad de Navarra, IDISNA, CIBEREHD, Pamplona, Navarra, Spain
| | - Michael C. Soulen
- Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | | | - Ricky A. Sharma
- NIHR University College London Hospitals Biomedical Research Centre, UCL Cancer Institute, University College London, London, UK
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23
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Cucchetti A, Cappelli A, Mosconi C, Zhong JH, Cescon M, Pinna AD, Golfieri R. Improving patient selection for selective internal radiation therapy of intra-hepatic cholangiocarcinoma: A meta-regression study. Liver Int 2017; 37:1056-1064. [PMID: 28177190 DOI: 10.1111/liv.13382] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2016] [Accepted: 01/30/2017] [Indexed: 01/27/2023]
Abstract
BACKGROUND & AIMS Selective internal radiation therapy (SIRT) is emerging as a potential therapy for unresectable intra-hepatic cholangiocarcinoma (iCCA) able to prolong life-expectancy. Aim of this study was to collect available literature meta-analyse data and results and investigate sources of heterogeneity through a meta-regression approach before suggesting SIRT as a valuable option. METHODS A systematic review of studies published until 1 September 2016 in PubMed and Scopus databases was performed. Patient survival was the primary outcome measure. Meta-analysis was performed using a random-effects model. Meta-regression was applied to investigate relationships existing between clinical and tumour features and the primary outcome. RESULTS Nine observational studies were included in the analysis involving 224 patients. The 1-, 2- and 3-year pooled survival estimates were 55.7%, 33.1% and 20.2%. Clinical and tumour characteristics showed medium-to-considerable heterogeneity (I2 >50%). Meta-regression analysis showed that determinants of best survivals were the presence of mass-forming iCCA type (median survival=19.9 months vs 8.1 months for the infiltrative type; P=.002) that also accounted for most of the heterogeneity between included studies (residual I2 =0); SIRT as first-line therapy (median survival=24 months vs 11.5 months for non-naïve patients; P=.048) and the adoption of concomitant chemotherapy (median survival 19.5 months vs 5.5 months in patients not receiving chemotherapy; P=.042). CONCLUSIONS There is considerable heterogeneity between studies highlighting that indications for SIRT are extremely varied. To ameliorate SIRT results naïve patients with mass-forming iCCA should be selected as the best candidates with the possibility of adding concomitant standard chemotherapy.
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Affiliation(s)
- Alessandro Cucchetti
- Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Alberta Cappelli
- Radiology Unit, Department of Digestive Disease and Internal Medicine, Sant'Orsola-Malpighi Hospital, Bologna, Italy
| | - Cristina Mosconi
- Radiology Unit, Department of Digestive Disease and Internal Medicine, Sant'Orsola-Malpighi Hospital, Bologna, Italy
| | - Jian-Hong Zhong
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Matteo Cescon
- Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Antonio D Pinna
- Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Rita Golfieri
- Radiology Unit, Department of Digestive Disease and Internal Medicine, Sant'Orsola-Malpighi Hospital, Bologna, Italy
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Mosconi C, Cappelli A, Ascanio S, Pettinari I, Modestino F, Renzulli M, Galaverni MC, Cucchetti A, Gramenzi A, Pettinato C, Golfieri R. Yttrium-90 microsphere radioembolization in unresectable intrahepatic cholangiocarcinoma. Future Oncol 2017; 13:1301-1310. [DOI: 10.2217/fon-2017-0022] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Intrahepatic cholangiocarcinoma is increasing in frequency worldwide, but radical surgical treatment is practicable in 30–40% of cases. The median survival without therapy is about 8 months, increased to 12 months in combination with systemic chemotherapy. Therefore, locoregional therapies, such as, radiofrequency ablation or transarterial chemoembolization have been employed. Radioembolization with yttrium-90 microspheres (90Y-TARE) is a novel intrarterial treatment which could be included in the armamentarium of treatment options, having shown higher median survival (up to 22 months) and low complication rates. Evidence-based algorithms for staging and allocation to treatment should be defined in the future, after robust results obtained through randomized controlled trials, thus establishing the exact role and timing of 90Y-TARE in the treatment protocol of unresectable intrahepatic cholangiocarcinoma.
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Affiliation(s)
- Cristina Mosconi
- Radiology Unit, Department of Diagnostic & Preventive Medicine, S Orsola-Malpighi University Hospital, Bologna, Italy
| | - Alberta Cappelli
- Radiology Unit, Department of Diagnostic & Preventive Medicine, S Orsola-Malpighi University Hospital, Bologna, Italy
| | - Salvatore Ascanio
- Radiology Unit, Department of Diagnostic & Preventive Medicine, S Orsola-Malpighi University Hospital, Bologna, Italy
| | - Irene Pettinari
- Radiology Unit, Department of Diagnostic & Preventive Medicine, S Orsola-Malpighi University Hospital, Bologna, Italy
| | - Francesco Modestino
- Radiology Unit, Department of Diagnostic & Preventive Medicine, S Orsola-Malpighi University Hospital, Bologna, Italy
| | - Matteo Renzulli
- Radiology Unit, Department of Diagnostic & Preventive Medicine, S Orsola-Malpighi University Hospital, Bologna, Italy
| | - Maria Cristina Galaverni
- Radiology Unit, Department of Diagnostic & Preventive Medicine, S Orsola-Malpighi University Hospital, Bologna, Italy
| | - Alessandro Cucchetti
- Department of Medical & Surgical Sciences, S.Orsola – Malpighi Hospital, Alma Mater Studiorum, University of Bologna, Italy
| | - Annagiulia Gramenzi
- Department of Medical & Surgical Sciences, Alma Mater Studiorum, University of Bologna, Italy
| | - Cinzia Pettinato
- Medical Physics Unit, Radiology Unit, S Orsola-Malpighi Hospital, Bologna, Italy
| | - Rita Golfieri
- Radiology Unit, Department of Diagnostic & Preventive Medicine, S Orsola-Malpighi University Hospital, Bologna, Italy
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Wang EA, Broadwell SR, Bellavia RJ, Stein JP. Selective internal radiation therapy with SIR-Spheres in hepatocellular carcinoma and cholangiocarcinoma. J Gastrointest Oncol 2017; 8:266-278. [PMID: 28480066 PMCID: PMC5401864 DOI: 10.21037/jgo.2016.11.08] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Accepted: 08/29/2016] [Indexed: 12/11/2022] Open
Abstract
Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) often present at stages where patients have limited treatment options. Use of selective internal radiation therapy (SIRT) with yttrium-90 (Y-90) resin microspheres has progressed as data increasingly speak to its utility in patients with both intermediate and late stage disease in these cancers. In anticipation of the pending completion of several prospective randomized controlled multicenter studies exploring the use of Y-90 resin microspheres in primary liver cancers, this article outlines mechanisms involved in SIRT administration and reviews key efficacy and safety data that are currently available in the literature involving use of this therapy in both HCC and ICC.
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Affiliation(s)
- Eric A Wang
- Charlotte Radiology, Carolinas Medical Center, Charlotte, NC, USA
| | | | - Ross J Bellavia
- Charlotte Radiology, Carolinas Medical Center, Charlotte, NC, USA
| | - Jeff P Stein
- Charlotte Radiology, Carolinas Medical Center, Charlotte, NC, USA
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26
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Savic LJ, Chapiro J, Geschwind JFH. Intra-arterial embolotherapy for intrahepatic cholangiocarcinoma: update and future prospects. Hepatobiliary Surg Nutr 2017; 6:7-21. [PMID: 28261591 DOI: 10.21037/hbsn.2016.11.02] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Intrahepatic cholangiocarcinoma (ICC) is a rare disease and carries a poor prognosis with surgery remaining the only curative treatment option. However, due to the late presentation of symptoms and close proximity of the tumors to central hepatic structures, only about 30% of patients are classified eligible to resection. As for palliative approaches, ICC constitutes a possible indication for loco-regional therapies (LRT). As such, intra-arterial therapies (IAT) are reported to be feasible, safe and effective in inducing tumor response in unresectable ICC. The paradigm of IAT is premised on the selective delivery of embolic, chemotherapeutic agents to the tumor via its feeding arteries, thus allowing dose escalation within the carcinoma and reduction of systemic toxicity. Conventional transcatheter arterial chemoembolization (cTACE) so far remains the most commonly used IAT modality. However, drug-eluting beads (DEB)-TACE was initiated with the idea of more selective targeting of the tumor owing to the combined embolizing as well as drug-eluting properties of the microspheres used in this setting. Moreover, radioembolization is performed by intra-arterial administration of very small spheres containing β-emitting yttrium-90 (Y90-RE) to the site of the tumor. Clinical evidence exists in support of survival benefits for IAT in the palliative treatment of ICC compared to surgery and systemic chemotherapy. As for combination regimens, cTACE, DEB-TACE and Y90-RE are reported to achieve conversion of patients to surgery in a sequential treatment planning and simultaneous IAT combinations may provide a therapeutic option for treatment escalation. Regarding the current status of literature, controlled randomized prospective trials to compare different IAT techniques and combination therapies as well as treatment recommendations for different IAT modalities are needed.
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Affiliation(s)
- Lynn Jeanette Savic
- Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, USA; ; Department of Diagnostic and Interventional Radiology, Universitätsmedizin Charité, Berlin, Germany
| | - Julius Chapiro
- Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, USA; ; Department of Diagnostic and Interventional Radiology, Universitätsmedizin Charité, Berlin, Germany
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Abstract
BACKGROUND Cholangiocarcinoma (CC) is the second most primary liver malignancy with increasing incidence in Western countries. Currently, surgical R0 resection is regarded as the only potentially curative treatment. The results of systemic chemotherapy and best supportive care (BSC) in patients with metastatic disease are often disappointing in regard to toxicity, oncologic efficacy, and overall survival. In current practice, the use of different locoregional therapies is increasingly more accepted. METHODS A review of the literature on locoregional therapies for intrahepatic cholangiocarcinoma (ICC) was undertaken. RESULTS There are no prospective randomized controlled trials. For localized ICC, either primary or recurrent, radiofrequency ablation (RFA) is by far the most commonly used thermal ablation modality. Thereby, a systematic review and meta-analysis reports major complication in 3.8% as well as 1-, 3-, and 5-year overall survival rates of 82, 47, and 24%, respectively. In selected patients (e.g. with a tumor diameter of ≤3 cm), oncologic efficacy and survival after RFA are comparable with surgical resection. For diffuse ICC, different transarterial therapies, either chemotherapy-based (hepatic artery infusion (HAI), transarterial chemoembolization (TACE)) or radiotherapy-based (transarterial radioembolization (TARE)), show extremely promising results. With regard to controlled trials (transarterial therapy versus systemic chemotherapy, BSC or no treatment), tumor control is virtually always better for transarterial therapies and very often accompanied by a dramatic survival benefit and improvement of quality of life. Of note, the latter is the case not only for patients without extrahepatic metastatic disease but also for those with liver-dominant extrahepatic metastatic disease. There are other locoregional therapies such as microwave ablation, irreversible electroporation, and chemosaturation; however, the current data support their use only in controlled trials or as last-line therapy. CONCLUSION Dedicated locoregional therapies are commonly used for primary and recurrent ICC as well as liver-only and liver-dominant extrahepatic metastatic disease. Currently, the best evidence and most promising results are available for RFA, HAI, TACE, and TARE. In cohort studies, the overall survival rates are similar to those obtained with surgery or systemic therapies. Prospective randomized controlled trials are warranted to compare safety and efficacy between different surgical, interventional, and systemic therapies, as well as their combinations.
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Affiliation(s)
- Christof M Sommer
- Clinic for Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany, Heilbronn, Germany; Clinic for Diagnostic and Interventional Radiology, Klinikum Stuttgart, Stuttgart, Germany, Heilbronn, Germany
| | - Hans U Kauczor
- Clinic for Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany, Heilbronn, Germany
| | - Philippe L Pereira
- Clinic for Radiology, Minimally Invasive Therapies and Nuclear Medicine, SLK Kliniken Heilbronn GmbH, Heilbronn, Germany
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Cucchetti A, Cappelli A, Ercolani G, Mosconi C, Cescon M, Golfieri R, Pinna AD. Selective Internal Radiation Therapy (SIRT) as Conversion Therapy for Unresectable Primary Liver Malignancies. Liver Cancer 2016; 5:303-311. [PMID: 27781202 PMCID: PMC5075901 DOI: 10.1159/000449341] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Many patients with primary liver cancers are not candidates for surgery, and systemic therapies are seldom effective. Selective internal radiation therapy (SIRT) has been shown to obtain partial and even complete response in unresectable primary tumors. As a "side effect", SIRT can induce contra-lateral liver hypertrophy. Tumor response to SIRT can be sufficient to allow disengagement from normal vital structures whose involvement is the cause of the initial unresectability. The contra-lateral hypertrophy can thereby increase the future liver remnant (FLR) volume to over the safe threshold so that extended hepatectomy can be performed. SUMMARY A review of the available literature was performed to assess the tumor response and liver hypertrophy that can be expected after SIRT, in order to delineate whether SIRTcan play a role in conversion therapy for resectability of primary liver malignancies. KEY MESSAGE Available data suggest that SIRT in unresectable hepatocellular and cholangiocellular carcinomas can provide a considerable down-sizing of the tumors to possibly allow resection. Hypertrophy of the contra-lateral lobe represents a favorable collateral effect that can help in achieving safer subsequent major hepatectomy. In patients whose FLR volume represents the only surgical concern, portal vein embolization remains the treatment of choice.
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Affiliation(s)
- Alessandro Cucchetti
- Department of Medical and Surgical Sciences–DIMEC, S.Orsola-Malpighi Hospital, Alma Mater Studiorum−University of Bologna, Bologna, Italy,*Alessandro Cucchetti, MD, Department of Medical and Surgical Sciences–DIMEC, S.Orsola-Malpighi, Hospital, Alma Mater Studiorum–University of Bologna, Via Massarenti 9, 40138 Bologna (Italy), Tel. +39 051 6363721, E-Mail
| | - Alberta Cappelli
- Radiology Unit, Department of Diagnostic and Preventive Medicine, S.Orsola-Malpighi Hospital, Bologna, Italy
| | - Giorgio Ercolani
- Department of Medical and Surgical Sciences–DIMEC, S.Orsola-Malpighi Hospital, Alma Mater Studiorum−University of Bologna, Bologna, Italy
| | - Cristina Mosconi
- Radiology Unit, Department of Diagnostic and Preventive Medicine, S.Orsola-Malpighi Hospital, Bologna, Italy
| | - Matteo Cescon
- Department of Medical and Surgical Sciences–DIMEC, S.Orsola-Malpighi Hospital, Alma Mater Studiorum−University of Bologna, Bologna, Italy
| | - Rita Golfieri
- Radiology Unit, Department of Diagnostic and Preventive Medicine, S.Orsola-Malpighi Hospital, Bologna, Italy
| | - Antonio Daniele Pinna
- Department of Medical and Surgical Sciences–DIMEC, S.Orsola-Malpighi Hospital, Alma Mater Studiorum−University of Bologna, Bologna, Italy
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29
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Mehta R, Cai K, Kumar N, Knuttinen MG, Anderson TM, Lu H, Lu Y. A Lesion-Based Response Prediction Model Using Pretherapy PET/CT Image Features for Y90 Radioembolization to Hepatic Malignancies. Technol Cancer Res Treat 2016; 16:620-629. [PMID: 27601017 DOI: 10.1177/1533034616666721] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
We present a probabilistic approach to identify patients with primary and secondary hepatic malignancies as responders or nonresponders to yttrium-90 radioembolization therapy. Recent advances in computer-aided detection have decreased false-negative and false-positive rates of perceived abnormalities; however, there is limited research in using similar concepts to predict treatment response. Our approach is driven by the goal of precision medicine to determine pretherapy fluorine-18-2-fluoro-2-deoxy-d-glucose positron emission tomography and computed tomography imaging parameters to facilitate the identification of patients who would benefit most from yttrium-90 radioembolization therapy, while avoiding complex and costly procedures for those who would not. Our algorithm seeks to predict a patient's response by discovering common co-occurring image patterns in the lesions of baseline fluorine-18-2-fluoro-2-deoxy-d-glucose positron emission tomography and computed tomography scans by extracting invariant shape and texture features. The extracted imaging features were represented as a distribution of each subject based on the bag-of-feature paradigm. The distribution was applied in a multinomial naive Bayes classifier to predict whether a patient would be a responder or nonresponder to yttrium-90 radioembolization therapy based on the imaging features of a pretherapy fluorine-18-2-fluoro-2-deoxy-d-glucose positron emission tomography and computed tomography scan. Comprehensive published criteria were used to determine lesion-based clinical treatment response based on fluorine-18-2-fluoro-2-deoxy-d-glucose positron emission tomography and computed tomography imaging findings. Our results show that the model is able to predict a patient with liver cancer as a responder or nonresponder to yttrium-90 radioembolization therapy with a sensitivity of 0.791 using extracted invariant imaging features from the pretherapy fluorine-18-2-fluoro-2-deoxy-d-glucose positron emission tomography and computed tomography test. The sensitivity increased to 0.821 when combining extracted invariant image features with variable features of tumor volume.
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Affiliation(s)
- Rahul Mehta
- 1 Department of Radiology, College of Medicine, University of Illinois Hospital & Health Sciences System, Chicago, IL, USA.,2 Department of Bioengineering, College of Medicine, University of Illinois Hospital & Health Sciences System, Chicago, IL, USA
| | - Kejia Cai
- 1 Department of Radiology, College of Medicine, University of Illinois Hospital & Health Sciences System, Chicago, IL, USA.,2 Department of Bioengineering, College of Medicine, University of Illinois Hospital & Health Sciences System, Chicago, IL, USA.,3 The Center for MR Research, College of Medicine, University of Illinois Hospital & Health Sciences System, Chicago, IL, USA
| | - Nishant Kumar
- 1 Department of Radiology, College of Medicine, University of Illinois Hospital & Health Sciences System, Chicago, IL, USA
| | - M Grace Knuttinen
- 1 Department of Radiology, College of Medicine, University of Illinois Hospital & Health Sciences System, Chicago, IL, USA
| | - Thomas M Anderson
- 1 Department of Radiology, College of Medicine, University of Illinois Hospital & Health Sciences System, Chicago, IL, USA
| | - Hui Lu
- 2 Department of Bioengineering, College of Medicine, University of Illinois Hospital & Health Sciences System, Chicago, IL, USA
| | - Yang Lu
- 1 Department of Radiology, College of Medicine, University of Illinois Hospital & Health Sciences System, Chicago, IL, USA
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30
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Clinical imaging of vascular disease in chronic kidney disease. Int Urol Nephrol 2016; 48:827-37. [PMID: 26898824 DOI: 10.1007/s11255-016-1240-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Accepted: 02/05/2016] [Indexed: 12/18/2022]
Abstract
Arterial wall calcification, once considered an incidental finding, is now known to be a consistent and strong predictor of cardiovascular events in patients with chronic renal insufficiency. It is also commonly encountered in radiologic examinations as an incidental finding. Forthcoming bench, translational, and clinical data seek to establish this and pre-calcification changes as surrogate imaging biomarkers for noninvasive prognostication and treatment follow-up. Emerging paradigms seek to establish vascular calcification as a surrogate marker of disease. Imaging of pre-calcification and decalcification events may prove more important than imaging of the calcification itself. Data-driven approaches to screening will be necessary to limit radiation exposure and prevent over-utilization of expensive imaging techniques.
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31
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Bagni O, Filippi L, Pelle G, Cianni R, Schillaci O. Total Lesion Glycolysis and Sequential (90)Y-Selective Internal Radiation Therapy in Breast Cancer Liver Metastases: Preliminary Results. Cancer Biother Radiopharm 2015; 30:421-6. [PMID: 26594900 DOI: 10.1089/cbr.2015.1877] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
To assess the prognostic role of total lesion glycolysis (TLG) in patients with breast cancer liver metastases (BCLM) after sequential lobar (90)Y-radioembolization ((90)Y-RE). Seventeen patients with bilobar BCLM underwent FDG PET/CT and TLG calculation before (90)Y-RE. The hepatic lobe with the highest TLG was treated in the first session. PET was performed 6 weeks postprocedure and decrease in TLG (ΔTLG) in the treated lobe was calculated before the second (90)Y administration. Subjects were divided in two groups (group 1: ΔTLG >50%, group 2: ΔTLG <50%). After the two consecutive (90)Y-therapies, patients underwent follow-up until death. Statistical analysis was performed to identify prognostic factors on overall survival (OS). After the first (90)Y administration, 10 cases showed a ΔTLG >50% and seven had a ΔTLG value <50%. After the two consecutive procedures, the mean OS for all patients was 13.5 ± 0.8 months. Subjects with a ΔTLG >50% and ΔTLG <50% had a mean OS of 16.4 ± 0.6 and 10.3 ± 0.4 months, respectively (p < 0.001). Cox regression analysis demonstrated hepatic tumor load (p = 0.048) and ΔTLG as the only significant (p = 0.005) predictors of survival. ΔTLG after the first (90)Y administration agrees with final outcome in BCLM patients after separate sequential lobar (90)Y-RE.
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Affiliation(s)
- Oreste Bagni
- 1 Department of Nuclear Medicine, Santa Maria Goretti Hospital , Latina, Italy
| | - Luca Filippi
- 1 Department of Nuclear Medicine, Santa Maria Goretti Hospital , Latina, Italy
| | - Giuseppe Pelle
- 2 Department of Interventional Radiology, Santa Maria Goretti Hospital , Latina, Italy
| | - Roberto Cianni
- 2 Department of Interventional Radiology, Santa Maria Goretti Hospital , Latina, Italy
| | - Orazio Schillaci
- 3 Department of Biomedicine and Prevention, University Tor Vergata , Rome, Italy
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Soydal C, Kucuk ON, Bilgic S, Ibis E. Radioembolization with 90Y resin microspheres for intrahepatic cholangiocellular carcinoma: prognostic factors. Ann Nucl Med 2015; 30:29-34. [DOI: 10.1007/s12149-015-1026-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2015] [Accepted: 08/28/2015] [Indexed: 12/28/2022]
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Kuei A, Saab S, Cho SK, Kee ST, Lee EW. Effects of Yttrium-90 selective internal radiation therapy on non-conventional liver tumors. World J Gastroenterol 2015; 21:8271-8283. [PMID: 26217079 PMCID: PMC4507097 DOI: 10.3748/wjg.v21.i27.8271] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2015] [Revised: 04/29/2015] [Accepted: 06/16/2015] [Indexed: 02/06/2023] Open
Abstract
The liver is a common site of metastasis, with essentially all metastatic malignancies having been known to spread to the liver. Nearly half of all patients with extrahepatic primary cancer have hepatic metastases. The severe prognostic implications of hepatic metastases have made surgical resection an important first line treatment in management. However, limitations such as the presence of extrahepatic spread or poor functional hepatic reserve exclude the majority of patients as surgical candidates, leaving chemotherapy and locoregional therapies as next best options. Selective internal radiation therapy (SIRT) is a form of catheter-based locoregional cancer treatment modality for unresectable tumors, involving trans-arterial injection of microspheres embedded with a radio-isotope Yttrium-90. The therapeutic radiation dose is selectively delivered as the microspheres permanently embed themselves within the tumor vascular bed. Use of SIRT has been conventionally aimed at treating primary hepatic tumors (hepatocellular carcinoma) or colorectal and neuroendocrine metastases. Numerous reviews are available for these tumor types. However, little is known or reviewed on non-colorectal or non-neuroendocrine primaries. Therefore, the aim of this paper is to systematically review the current literature to evaluate the effects of Yttrium-90 radioembolization on non-conventional liver tumors including those secondary to breast cancer, cholangiocarcinoma, ocular and percutaneous melanoma, pancreatic cancer, renal cell carcinoma, and lung cancer.
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Seidensticker R, Ricke J, Seidensticker M. Integration of chemoembolization and radioembolization into multimodal treatment of cholangiocarcinoma. Best Pract Res Clin Gastroenterol 2015; 29:319-32. [PMID: 25966431 DOI: 10.1016/j.bpg.2015.02.009] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2014] [Accepted: 02/07/2015] [Indexed: 02/07/2023]
Abstract
Over the last decade radioembolization and transarterial chemoembolization have been shown to be effective in unresectable intrahepatic cholangiocellular carcinoma. Unfortunately, up to now the evidence is not high with most of the conclusions drawn from single center retrospective analyses with small sample sizes treated in the salvage situation. However, the results are promising and suggest a survival benefit in the treatment of unresectable cholangiocellular carcinoma, even in an advanced stage with extrahepatic disease. In the following, available results of the treatment of unresectable cholangiocellular carcinoma by radioembolization and transarterial chemoembolization will be summarized. Special attention will be given to prognostic factors and efficacy as measured by response criteria. The potential integration of these therapies into multimodal treatment concepts will be discussed with focus on the intensification of therapy and a staged concept of therapy.
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Affiliation(s)
- Ricarda Seidensticker
- Universitätsklinikum Magdeburg, Klinik für Radiologie und Nuklearmedizin, Magdeburg, Germany; Zentrum für Gastrointestinale Tumoren, ZeGIT, Magdeburg, Germany; Deutsche Akademie für Mikrotherapie, DAfMT, Germany.
| | - Jens Ricke
- Universitätsklinikum Magdeburg, Klinik für Radiologie und Nuklearmedizin, Magdeburg, Germany; Zentrum für Gastrointestinale Tumoren, ZeGIT, Magdeburg, Germany; Deutsche Akademie für Mikrotherapie, DAfMT, Germany
| | - Max Seidensticker
- Universitätsklinikum Magdeburg, Klinik für Radiologie und Nuklearmedizin, Magdeburg, Germany; Zentrum für Gastrointestinale Tumoren, ZeGIT, Magdeburg, Germany; Deutsche Akademie für Mikrotherapie, DAfMT, Germany
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35
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18F-FDG PET-derived parameters as prognostic indices in hepatic malignancies after 90Y radioembolization: is there a role? Eur J Nucl Med Mol Imaging 2014; 42:367-9. [PMID: 25476259 DOI: 10.1007/s00259-014-2966-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2014] [Accepted: 11/25/2014] [Indexed: 10/24/2022]
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