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LaCasce AS, Dockter T, Ruppert AS, Kostakoglu L, Schöder H, Hsi E, Bogart J, Cheson B, Wagner-Johnston N, Abramson J, Blum K, Leonard JP, Bartlett NL. Positron Emission Tomography-Adapted Therapy in Bulky Stage I/II Classic Hodgkin Lymphoma: CALGB 50801 (Alliance). J Clin Oncol 2023; 41:1023-1034. [PMID: 36269899 PMCID: PMC9928671 DOI: 10.1200/jco.22.00947] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 08/01/2022] [Accepted: 08/10/2022] [Indexed: 11/20/2022] Open
Abstract
PURPOSE Patients with bulky stage I/II classic Hodgkin lymphoma (cHL) are typically treated with chemotherapy followed by radiation. Late effects associated with radiotherapy include increased risk of second cancer and cardiovascular disease. We tested a positron emission tomography (PET)-adapted approach in patients with bulky, early-stage cHL, omitting radiotherapy in patients with interim PET-negative (PET-) disease and intensifying treatment in patients with PET-positive (PET+) disease. METHODS Eligible patients with bulky disease (mass > 10 cm or 1/3 the maximum intrathoracic diameter on chest x-ray) received two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by interim fluorodeoxyglucose PET (PET2). Patients with PET2-, defined as 1-3 on the 5-point scale, received four additional cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine. Patients with PET2+ received four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone followed by 30.6 Gy involved-field radiation. RESULTS Of 94 evaluable patients, 53% were female with median age 30 years (range, 18-58 years). Eight-five (90%) had stage II disease, including 48 (51%) with stage IIB/IIBE. Seventy-eight (78%) were PET2- and 21 (22%) were PET2+. The predominant toxicity was neutropenia, with 9% of patients developing febrile neutropenia and one developing sepsis. The primary end point of 3-year progression-free survival (PFS) was 93.1% in PET2- and 89.7% in PET2+ patients. Three-year overall survival was 98.6% and 94.4%, respectively. The estimated hazard ratio comparing PFS of patients with PET2+ and patients with PET2- was 1.03 (85% upper bound 2.38) and was significantly less than the null hypothesis of 4.1 (one-sided P = .04). CONCLUSION Our study of PET-adapted therapy in bulky stage I/II cHL met its primary goal and was associated with an excellent 3-year PFS rate of 92.3% in all patients, with the majority being spared radiotherapy and exposure to intensified chemotherapy.
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Affiliation(s)
| | - Travis Dockter
- Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN
| | - Amy S. Ruppert
- Alliance Statistics and Data Management Center, The Ohio State University, Columbus, OH
| | | | - Heiko Schöder
- Memorial Sloan Kettering Cancer Center, New York, NY
| | - Eric Hsi
- Wake Forest University Health Sciences, Winston-Salem, NC
| | - Jeffrey Bogart
- State University of New York Upstate Medical University Syracuse-Health Science Center, Syracuse, NY
| | - Bruce Cheson
- Scientific Advisor, Lymphoma Research Foundation, New York, NY
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2
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Weil CR, Parsons MJ, Hutten RJ, Lew FH, Johnson SB, Gaffney DK, Tao R. Patterns of care and outcomes of early stage I-II Hodgkin lymphoma treated with or without radiation therapy. Leuk Lymphoma 2022; 63:2847-2857. [PMID: 35904407 DOI: 10.1080/10428194.2022.2105325] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Omission of radiotherapy in the upfront management of early-stage classic Hodgkin lymphoma (cHL) has become more common with time. We report patterns of care and outcomes of stage I-II cHL treated with chemotherapy (CT) only versus CT and radiotherapy (combined modality therapy, CMT). From the National Cancer Database, we identified 28,327 early-stage cHL patients treated with CT (n = 15,798) or CMT (n = 12,529) from 2004 to 2018. CMT utilization declined over the period from 58% to 34%. With median follow-up of 6.2 years, the 5- and 10-year overall survival for CT versus CMT was 93.3% versus 96.9% (p < 0.001) and 88.7% versus 93.5% (p < 0.001), respectively. On multivariable analysis, uninsured (OR 0.75, p < 0.001) and Black patients (OR 0.86, p = 0.02) were less likely to receive CMT, and treatment with CT was predictive of death (OR 2.0, p < 0.001). This report highlights real-world outcomes in early-stage cHL, with worse survival with CT and notable disparities in CMT utilization.
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Affiliation(s)
- Christopher R Weil
- Department of Radiation Oncology, University of Utah School of Medicine, Salt Lake City, UT, USA.,Elson S. Floyd College of Medicine, Washington State University, Spokane, WA, USA
| | - Matthew J Parsons
- Department of Radiation Oncology, University of Utah School of Medicine, Salt Lake City, UT, USA
| | - Ryan J Hutten
- Department of Radiation Oncology, University of Utah School of Medicine, Salt Lake City, UT, USA
| | - Felicia H Lew
- Elson S. Floyd College of Medicine, Washington State University, Spokane, WA, USA
| | - Skyler B Johnson
- Department of Radiation Oncology, University of Utah School of Medicine, Salt Lake City, UT, USA
| | - David K Gaffney
- Department of Radiation Oncology, University of Utah School of Medicine, Salt Lake City, UT, USA
| | - Randa Tao
- Department of Radiation Oncology, University of Utah School of Medicine, Salt Lake City, UT, USA
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Hamid MS, Rutherford SC, Jang H, Kim S, Patel K, Bartlett NL, Malecek MK, Watkins MP, Maddocks KJ, Bond DA, Feldman TA, Magarelli G, Advani RH, Spinner MA, Evens AM, Shah M, Ahmed S, Stephens DM, Allen P, Tees MT, Karmali R, Cheson BD, Yazdy MS, Strouse C, Bailey NA, Pagel JM, Ramchandren R. Outcomes Among Classical Hodgkin Lymphoma Patients After an Interim PET Scan: A Real-World Experience. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2022; 22:e435-e442. [PMID: 35093285 DOI: 10.1016/j.clml.2021.12.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 11/17/2021] [Accepted: 12/18/2021] [Indexed: 06/14/2023]
Abstract
INTRODUCTION The utility of dose escalation after positive positron emission tomography following 2 cycles of ABVD (PET2) for Hodgkin Lymphoma (HL) remains controversial. We describe the United States real-world practice patterns for PET2 positive patients. PATIENTS AND METHODS Data was collected from 15 sites on PET2 positive HL patients after receiving frontline treatment between January, 2015 and June, 2019. Descriptive analyses between those with therapy change and those continuing initial therapy were assessed. RESULTS A total of 129 patients were identified; 111 (86%) were treated with ABVD therapy and 18 (14%) with an alternate regimen. At PET2 assessment, 74.4% (96/129) had Deauville score (DS) 4 and 25.6% (33/129) had DS 5. Of the 66 limited stage (LS) patients with PET2 DS score of 4/5, 77.3% (51/66) continued initial therapy and 22.7% (15/66) changed to escalated therapy. The 12-month progression-free survival (PFS) for DS 4/5 LS patients was 67.0% (95% CI; 54.9-81.7) for patients without escalation compared with 51.4% (95% CI; 30.8-85.8) for those who escalated. Of the 63 DS 4/5 patients with advanced stage (AS) disease, 76.2% (48/63) continued initial therapy and 23.8% (15/63) changed to escalated therapy. The 12-month PFS for DS 4/5 AS patients was 38.3% (95% CI: 26.3%-55.7%) for patients without escalation compared with 57.1% (95% CI: 36.3-89.9) for those with escalation. CONCLUSION A minority of PET2 positive HL patients undergo therapy escalation and outcomes remain overall suboptimal. Improved prognostics markers and better therapeutics are required to improve outcomes for high-risk PET2 positive HL patients.
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Affiliation(s)
| | | | | | | | | | - Nancy L Bartlett
- Washington University Medical University at St. Louis, St. Louis, MO
| | - Mary-Kate Malecek
- Washington University Medical University at St. Louis, St. Louis, MO
| | - Marcus P Watkins
- Washington University Medical University at St. Louis, St. Louis, MO
| | - Kami J Maddocks
- The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH
| | - David A Bond
- The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH
| | - Tatyana A Feldman
- John Theurer Cancer Center at Hackensack Meridian Health, Hackensack, NJ
| | - Gabriela Magarelli
- John Theurer Cancer Center at Hackensack Meridian Health, Hackensack, NJ
| | | | | | - Andrew M Evens
- Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
| | - Mansi Shah
- Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
| | | | | | - Pamela Allen
- Winship Cancer Institute at Emory University, Atlanta, GA
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Jennane S, Ababou M, El Haddad M, Ait Sahel O, Mahtat EM, El Maaroufi H, Doudouh A, Doghmi K. Bleomycin-Induced Lung Toxicity in Hodgkin's Lymphoma: Risk Factors in the Positron Emission Tomography Era. Cureus 2022; 14:e23993. [PMID: 35419251 PMCID: PMC8994685 DOI: 10.7759/cureus.23993] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/09/2022] [Indexed: 12/01/2022] Open
Abstract
Introduction Bleomycin is a major antimitotic agent in the first-line treatment for Hodgkin's lymphoma. The main limitation of its use is its pulmonary toxicity. The objectives of this study are to find out the risk factors for the occurrence of bleomycin-induced lung toxicity in patients with Hodgkin's lymphoma and, on the other hand, to determine if positron emission tomography scan is a reliable means of early detection of this toxicity. Methods This is a retrospective study conducted in the clinical Hematology Department of Mohammed V Military Instruction Hospital, Rabat, Morocco. All patients with Hodgkin's lymphoma and treated with a bleomycin-based chemotherapy were included. The impact of different clinical and biological factors on the risk of bleomycin-induced lung toxicity occurrence was assessed using univariate and multivariate logistic regression. The benefit of positron emission tomography, usually performed as part of the re-assessment of Hodgkin’s lymphoma after two and four cycles, has been evaluated in the detection of bleomycin-induced lung toxicity. Results Among 124 patients included in the study, 18 (14.5%) patients experienced bleomycin-induced lung toxicity. On multivariate analysis, smoking (p = 0.038) and the use of the ABVD regimen (doxorubicin, bleomycin, vinblastine, and dacarbazine) compared to the escalated BEACOPPe regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) (p = 0.018) were statistically significant risk factors. After two and four courses of therapy, the positron emission tomography was able to predict the occurrence of bleomycin-induced lung toxicity before the appearance of clinical symptoms only in 36.4 % and 12.5% of patients, respectively. Conclusion Studies to identify risk factors for the development of bleomycin-induced lung toxicity are crucial to reduce toxicity in the treatment of Hodgkin's lymphoma. However, two- and four-cycle positron emission tomography scans cannot be considered as a reliable means of early detection of this toxicity.
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Sánchez-Valledor LF, Habermann TM, Murrieta-Alvarez I, Córdova-Ramírez AC, Rivera-Álvarez M, León-Peña A, Cantero-Fortiz Y, Olivares-Gazca JC, Ruiz-Delgado GJ, Ruiz-Argüelles GJ. Long-term results of the treatment of Hodgkin's lymphoma in a resource-constrained setting: Real-world data from a single center. World J Clin Oncol 2021; 12:800-807. [PMID: 34631443 PMCID: PMC8479346 DOI: 10.5306/wjco.v12.i9.800] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Revised: 05/17/2021] [Accepted: 08/09/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The outcomes of Hodgkin´s lymphoma (HL) in México have not been widely reported. Simplified and affordable treatments have been adopted in middle-income countries. AIM The aim was to evaluate long-used therapies for HL in México in a long-term basis. METHODS In a 34-year time period, 88 patients with HL were treated at a single institution in México. Patients were treated with adriamycin bleomycin vinblastine and dacarbazine (ABVD) or mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). Relapsed or refractory patients were given ifosfamide, carboplatin, and etoposide (ICE) followed by autologous or allogeneic stem cell transplants. RESULTS Thirty-seven women and 51 men were included; the median age was 29 years. Patients were followed for a mean of 128 mo. The 310-mo overall survival (OS) was 83% for patients treated with MOPP and 88% for those treated with ABVD. The OS of patients who received autologous stem cell transplantation was 76% (330 mo) vs 93% (402 mo) in those who did not. CONCLUSION HL may be less aggressive in Mexican population than in Caucasians. Combined chemotherapy renders acceptable results, regardless of clinical stage.
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Affiliation(s)
| | - Thomas M Habermann
- Department of Medicine, Division of Hematology, Mayo Clinical and Mayo Foundation, Rochester, MN 55905, United States
| | | | | | | | - Andrés León-Peña
- Centro de Hematología y Medicina Interna, Clínica Ruiz, Puebla 72530, Mexico
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6
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Hall MD, Terezakis SA, Lucas JT, Gallop-Evans E, Dieckmann K, Constine LS, Hodgson D, Flerlage JE, Metzger ML, Hoppe BS. Radiotherapy across pediatric Hodgkin lymphoma research group protocols: a report from the Staging, Evaluation, and Response Criteria Harmonization (SEARCH) for childhood, adolescent, and young adult Hodgkin lymphoma (CAYAHL) Group. Int J Radiat Oncol Biol Phys 2021; 112:317-334. [PMID: 34390770 PMCID: PMC8802654 DOI: 10.1016/j.ijrobp.2021.07.1716] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 07/23/2021] [Accepted: 07/31/2021] [Indexed: 01/17/2023]
Affiliation(s)
- Matthew D Hall
- Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA.
| | | | - John T Lucas
- Department of Radiation Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA
| | - Eve Gallop-Evans
- Department of Clinical Oncology, Velindre Cancer Centre, Cardiff, Wales, United Kingdom
| | - Karin Dieckmann
- Department of Radiation Oncology, Medical University of Vienna, Vienna, Austria
| | - Louis S Constine
- Department of Radiation Oncology and Pediatrics, University of Rochester Medical Center, Rochester, NY, USA
| | - David Hodgson
- Department of Radiation Oncology, University of Toronto, Toronto, Alberta, Canada
| | - Jamie E Flerlage
- Department of Pediatric Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA
| | - Monika L Metzger
- Department of Pediatric Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA
| | - Bradford S Hoppe
- Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, USA
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7
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Habermann TM, Khurana A, Lentz R, Schmitz JJ, von Bormann AG, Young JR, Hunt CH, Christofferson SN, Nowakowski GS, McCullough KB, Horna P, Wood AJ, Macon WR, Kurtin PJ, Lester SC, Stafford SL, Chamarthy U, Khan F, Ansell SM, King RL. Analysis and impact of a multidisciplinary lymphoma virtual tumor board. Leuk Lymphoma 2020; 61:3351-3359. [PMID: 32967496 DOI: 10.1080/10428194.2020.1817432] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
The aim is to prospectively evaluate the impact of a multidisciplinary lymphoma virtual tumor board. The utility of multi-site interactive lymphoma-specific tumor boards has not been reported. The Mayo Clinic Lymphoma Tumor Board is a component of the International Mayo Clinic Care Network (MCCN). The format includes the clinical case presentation, presentation of radiology and hematopathology findings by the appropriate subspecialist, proposed treatment options, review of the literature pertinent to the case, pharmacy contributions, and discussion followed by recommendations. Three hundred and nine consecutive highly selected real-time cases with a diagnosis of lymphoma were presented at the Mayo Clinic Lymphoma Tumor Board from January 2014 to June 2018 and decisions were prospectively tracked to assess its impact on the treatment decisions. A total of 309 cases were prospectively evaluated. One hundred and forty (45.3%) cases had some changes made or recommended. The total changes suggested were 179, as some cases had more than one recommendation. There were 93 (30%) clinical management recommendations, 45 (14.6%) additional testing recommendations, 29 (9.4%) pathology changes, and 6 (1.9%) radiology changes. In an electronic evaluation process, 93% of the responders reported an improvement in knowledge and competence, and 100% recommended no change in format of the board. A multidisciplinary lymphoma tumor board approach was found to have a meaningful impact on lymphoma patients while enhancing interdisciplinary interactions and education for multiple levels of the clinical care team.
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Affiliation(s)
- Thomas M Habermann
- Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Arushi Khurana
- Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Ruth Lentz
- Division of Hematology, Department of Nursing, Mayo Clinic, Rochester, MN, USA
| | - John J Schmitz
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | | | - Jason R Young
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | | | | | | | | | - Pedro Horna
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Adam J Wood
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - William R Macon
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Paul J Kurtin
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Scott C Lester
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA
| | - Scott L Stafford
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA
| | - Ushrasree Chamarthy
- Department of Medical Oncology and Hematology, Sparrow Cancer Center, Lansing, MI, USA
| | - Faraz Khan
- Department of Hematology-Oncology, American Hospital Dubai, Dubai, United Arab Emirates
| | - Stephen M Ansell
- Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Rebecca L King
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
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Hoppe BS, Mailhot Vega RB, Mendenhall NP, Sandler ES, Slayton WB, Katzenstein H, Joyce MJ, Li Z, Flampouri S. Irradiating Residual Disease to 30 Gy with Proton Therapy in Pediatric Mediastinal Hodgkin Lymphoma. Int J Part Ther 2020; 6:11-16. [PMID: 32582815 PMCID: PMC7302731 DOI: 10.14338/ijpt-19-00077.1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Accepted: 03/05/2020] [Indexed: 11/24/2022] Open
Abstract
Background: Local relapse is a predominant form of recurrence among pediatric patients with Hodgkin lymphoma (PHL). Although PHL radiotherapy doses have been approximately 20 Gy, adults with Hodgkin lymphoma receiving 30 to 36 Gy experience fewer in-field relapses. We investigated the dosimetric effect of such a dose escalation to the organs at risk (OARs). Materials and Methods: Ten patients with PHL treated with proton therapy to 21 Gy involved-site radiation therapy (ISRT21Gy) were replanned to deliver 30 Gy by treating the ISRT to 30 Gy (ISRT30Gy), delivering 21 Gy to the ISRT plus a 9-Gy boost to postchemotherapy residual volume (rISRTboost), and delivering 30 Gy to the residual ISRT target only (rISRT30Gy). Radiation doses to the OARs were compared. Results: The ISRT30Gy escalated the dose to the target by 42% but also to the OARs. The rISRTboost escalated the residual target dose by 42%, and the OAR dose by only 17% to 26%. The rISRT30Gy escalated the residual target dose by 42% but reduced the OAR dose by 25% to 46%. Conclusion: Boosting the postchemotherapy residual target dose to 30Gy can allow for dose escalation with a slight OAR dose increase. Treating the residual disease for the full 30Gy, however, would reduce the OAR dose significantly compared with ISRT21Gy. Studies should evaluate these strategies to improve outcomes and minimize the late effects.
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Affiliation(s)
- Bradford S Hoppe
- Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, USA
| | | | - Nancy P Mendenhall
- Department of Radiation Oncology, University of Florida, Jacksonville, FL, USA
| | - Eric S Sandler
- Division of Pediatric Hematology and Oncology, Department of Pediatrics, Nemours Children's Specialty Care, Jacksonville, FL, USA
| | - William B Slayton
- Department of Pediatric Hematology/Oncology, University of Florida, Gainesville, FL, USA
| | - Howard Katzenstein
- Division of Pediatric Hematology and Oncology, Department of Pediatrics, Nemours Children's Specialty Care, Jacksonville, FL, USA
| | - Michael J Joyce
- Division of Pediatric Hematology and Oncology, Department of Pediatrics, Nemours Children's Specialty Care, Jacksonville, FL, USA
| | - Zuofeng Li
- Department of Radiation Oncology, University of Florida, Jacksonville, FL, USA
| | - Stella Flampouri
- Department of Radiation Oncology, Emory University, Atlanta, GA, USA
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9
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Hoppe RT, Advani RH, Ai WZ, Ambinder RF, Armand P, Bello CM, Benitez CM, Bierman PJ, Boughan KM, Dabaja B, Gordon LI, Hernandez-Ilizaliturri FJ, Herrera AF, Hochberg EP, Huang J, Johnston PB, Kaminski MS, Kenkre VP, Khan N, Lynch RC, Maddocks K, McConathy J, McKinney M, Metzger M, Morgan D, Mulroney C, Rabinovitch R, Rosenspire KC, Seropian S, Tao R, Winter JN, Yahalom J, Burns JL, Ogba N. Hodgkin Lymphoma, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2020; 18:755-781. [PMID: 32502987 DOI: 10.6004/jnccn.2020.0026] [Citation(s) in RCA: 88] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The NCCN Clinical Practice Guidelines in Oncology for Hodgkin Lymphoma (HL) provide recommendations for the management of adult patients with HL. The NCCN panel meets at least annually to review comments from reviewers within their institutions, examine relevant data, and reevaluate and update their recommendations. Current management of classic HL involves initial treatment with chemotherapy alone or combined modality therapy followed by restaging with PET/CT to assess treatment response. Overall, the introduction of less toxic and more effective regimens has significantly advanced HL cure rates. This portion of the NCCN Guidelines focuses on the management of classic HL.
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Affiliation(s)
| | | | - Weiyun Z Ai
- 2UCSF Helen Diller Family Comprehensive Cancer Center
| | | | | | | | | | | | - Kirsten M Boughan
- 7Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | | | - Leo I Gordon
- 9Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | | | | | - Jiayi Huang
- 13Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
| | | | | | | | | | - Ryan C Lynch
- 18Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
| | - Kami Maddocks
- 19The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | | | | | - Monika Metzger
- 22St. Jude Children's Research Hospital/The University of Tennessee Health Science Center
| | | | | | | | | | | | - Randa Tao
- 28Huntsman Cancer Institute at the University of Utah
| | - Jane N Winter
- 9Robert H. Lurie Comprehensive Cancer Center of Northwestern University
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10
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Weil CR, Qian Y, Von Eyben R, Daadi SE, Corbelli KS, Rosenberg SA, Advani RH, Hoppe RT. Long-term outcomes of patients with unfavorable stage I-II classic Hodgkin lymphoma treated with Stanford V chemotherapy and limited field irradiation. Leuk Lymphoma 2020; 61:2428-2434. [PMID: 32476541 DOI: 10.1080/10428194.2020.1768385] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Management of stage I-II unfavorable risk Hodgkin lymphoma (HL) strives to reduce toxicity while maintaining tumor control. Compared to ABVD or BEACOPP, Stanford V chemotherapy contains less doxorubicin and bleomycin. We report long-term outcomes of patients with stage I-II classic HL with European risk factors treated with Stanford V combined modality therapy (CMT). From our institutional cancer registry, we identified 168 patients with ≥1 European risk factor treated with 8-12 weeks of Stanford V CMT and consolidative radiotherapy between 1990 and 2016. Outcomes were analyzed after classification by EORTC and GHSG unfavorable criteria. With median follow-up of 8.4 years, 10-year overall survival and progression-free survival for the entire cohort were 95% and 88%, respectively. Thirteen of 18 relapses were salvaged successfully. There were no cases of MDS or AML after primary therapy. Long-term outcomes of stage I-II unfavorable risk HL treated with Stanford V CMT are comparable to ABVD or BEACOPP regimens.
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Affiliation(s)
- Christopher R Weil
- Department of Radiation Oncology, University of Utah School of Medicine, Salt Lake City, UT, USA
| | - Yushen Qian
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA
| | - Rie Von Eyben
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA
| | - Sarah E Daadi
- Department of Medicine, Division of Medical Oncology, Stanford University School of Medicine, Stanford, CA, USA
| | - Karen S Corbelli
- Department of Medicine, Division of Medical Oncology, Stanford University School of Medicine, Stanford, CA, USA
| | - Saul A Rosenberg
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA.,Department of Medicine, Division of Medical Oncology, Stanford University School of Medicine, Stanford, CA, USA
| | - Ranjana H Advani
- Department of Medicine, Division of Medical Oncology, Stanford University School of Medicine, Stanford, CA, USA
| | - Richard T Hoppe
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA
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11
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Lynch RC, Sundaram V, Desai M, Henry S, Wood D, Daadi S, Hoppe RT, Advani R. Utility of Routine Surveillance Laboratory Testing in Detecting Relapse in Patients With Classic Hodgkin Lymphoma in First Remission: Results From a Large Single-Institution Study. JCO Oncol Pract 2020; 16:e902-e911. [PMID: 32369413 DOI: 10.1200/jop.19.00733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
PURPOSE Classic Hodgkin lymphoma is highly curable with contemporary therapy. Although the limited role of surveillance imaging to detect early relapse for patients in complete remission at the end of therapy is well established, there is a paucity of data regarding role of laboratory testing in this setting. METHODS Patients with newly diagnosed classic Hodgkin lymphoma uniformly treated with the Stanford V regimen from 1998-2014 and in complete remission for at least 3 months were identified in a single-center institutional database. Laboratory tests categorized by Common Terminology Criteria for Adverse Events v4.03 as grade 2 or higher were considered abnormal. Primary analysis included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of surveillance laboratory tests for predicting relapse in the first 3 years after end of treatment. RESULTS Among 235 eligible patients, 24 (10.2%) patients ultimately relapsed. In the first 3 years after end of therapy, the mean number of surveillance blood draws per patient was 7.1, (range, 1-13). These 1,661 surveillance blood draws included 4,684 individual laboratory tests, comprising 1,609 CBCs, 1,578 metabolic panels, and 1,497 erythrocyte sedimentation rates. None of the biopsies confirming relapses were prompted by any abnormal laboratory finding. The sensitivity of any surveillance laboratory test for detecting relapse within 3 years of end of treatment was 72.7% (95% CI, 49.8% to 89.3%), specificity 22.6% (95% CI, 17.2% to 28.9%), yielding a PPV of 8.9% (95% CI, 7.0% to 11.3%) and NPV of 88.9% (95% CI, 79% to 94%). CONCLUSION Our study found limited clinically meaningful utility for routine surveillance laboratory testing in detecting relapse in patients with complete remission at end of treatment. Our results warrant consideration of modifications to current practice guidelines.
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Affiliation(s)
- Ryan C Lynch
- Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA.,Fred Hutchinson Cancer Research Center, Seattle, WA.,Division of Oncology, Department of Medicine, Stanford University, Stanford, CA
| | - Vandana Sundaram
- Quantitative Sciences Unit, Stanford University School of Medicine, Palo Alto, CA
| | - Manisha Desai
- Quantitative Sciences Unit, Stanford University School of Medicine, Palo Alto, CA
| | - Solomon Henry
- Stanford University School of Medicine, Stanford, CA
| | - Douglas Wood
- Stanford University School of Medicine, Stanford, CA
| | | | - Richard T Hoppe
- Department of Radiation Oncology, Stanford University, Stanford, CA
| | - Ranjana Advani
- Department of Medicine, Stanford University, Stanford, CA
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12
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Spinner MA, Advani RH, Connors JM, Azzi J, Diefenbach C. New Treatment Algorithms in Hodgkin Lymphoma: Too Much or Too Little? Am Soc Clin Oncol Educ Book 2018; 38:626-636. [PMID: 30231319 DOI: 10.1200/edbk_200679] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Hodgkin lymphoma treatment continues to evolve as new means of assessing response to treatment, new appreciation of important risk factors, and more effective therapeutic agents become available. Treatment algorithms integrating functional imaging now provide the opportunity to modify therapy during its delivery, allowing adjustment of duration and intensity of chemotherapy and rationale identification of patients who may benefit from the addition of therapeutic irradiation. Novel agents, including the antibody drug conjugate brentuximab vedotin and checkpoint inhibitors such as nivolumab and pembrolizumab can improve the effectiveness of treatment while keeping toxicity within acceptable limits. Carefully designed clinical trials permit the identification of superior approaches in which efficacy is enhanced and toxicity minimized. Clinicians treating patients with Hodgkin lymphoma now have access to novel treatment approaches, which will require detailed assessment of each patient and careful discussion of the goals and risks of treatment at the time of planning primary treatment, again during delivery of that treatment as data indicating ongoing effectiveness become available, at the conclusion of initial intervention, and, when the need arises, at the time of recurrence of disease.
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Affiliation(s)
- Michael A Spinner
- From the Department of Medicine, Division of Oncology, Stanford University, Stanford, CA; BC Cancer Centre for Lymphoid Cancer and University of British Columbia, Vancouver, BC, Canada; Perlmutter Cancer Center at NYU Langone Health, New York, NY
| | - Ranjana H Advani
- From the Department of Medicine, Division of Oncology, Stanford University, Stanford, CA; BC Cancer Centre for Lymphoid Cancer and University of British Columbia, Vancouver, BC, Canada; Perlmutter Cancer Center at NYU Langone Health, New York, NY
| | - Joseph M Connors
- From the Department of Medicine, Division of Oncology, Stanford University, Stanford, CA; BC Cancer Centre for Lymphoid Cancer and University of British Columbia, Vancouver, BC, Canada; Perlmutter Cancer Center at NYU Langone Health, New York, NY
| | - Jacques Azzi
- From the Department of Medicine, Division of Oncology, Stanford University, Stanford, CA; BC Cancer Centre for Lymphoid Cancer and University of British Columbia, Vancouver, BC, Canada; Perlmutter Cancer Center at NYU Langone Health, New York, NY
| | - Catherine Diefenbach
- From the Department of Medicine, Division of Oncology, Stanford University, Stanford, CA; BC Cancer Centre for Lymphoid Cancer and University of British Columbia, Vancouver, BC, Canada; Perlmutter Cancer Center at NYU Langone Health, New York, NY
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13
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Balancing risk and benefit in early-stage classical Hodgkin lymphoma. Blood 2018; 131:1666-1678. [DOI: 10.1182/blood-2017-10-772665] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Accepted: 02/07/2018] [Indexed: 01/23/2023] Open
Abstract
Abstract
With defined chemotherapy and radiotherapy (RT) and risk-adapted treatment, early-stage classical Hodgkin lymphoma (HL) has become curable in a majority of patients. Hence, a major current goal is to reduce treatment-related toxicity while maintaining long-term disease control. Patients with early-stage favorable disease (ie, limited stage without risk factors [RFs]) are frequently treated with 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (2×ABVD) followed by 20-Gy involved-field or involved-site RT (IF/ISRT). In patients with early-stage unfavorable disease (ie, limited stage with RFs), 4 cycles of chemotherapy are usually consolidated with 30-Gy IF/ISRT. Compared with 4×ABVD, 2 cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (2×BEACOPPescalated) followed by 2×ABVD improved 5-year progression-free survival (PFS), with similar 5-year overall survival. Recently, treatment strategies based on [18F]fluorodeoxyglucose positron emission tomography (PET) response were evaluated. In early-stage unfavorable HL, a majority of patients achieved a negative interim PET after 2×ABVD and an excellent outcome after 4×ABVD, whereas in those with a positive interim PET, 2×BEACOPPescalated improved 5-year PFS. Furthermore, a PET-guided RT approach was evaluated to decrease long-term toxicity. Although both the RAPID and H10 trials reported poorer disease control without RT, PET-guided omission of RT can constitute a valid therapeutic option in patients with an increased risk of RT-associated toxicity (eg, because of sex, age, or disease localization). Implementation of drugs such as the anti-CD30 antibody-drug conjugate brentuximab vedotin or the anti–programmed death 1 antibodies nivolumab or pembrolizumab might allow further reduction of overall mortality and improve quality of life in affected patients.
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14
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Allen PB, Gordon LI. Frontline Therapy for Classical Hodgkin Lymphoma by Stage and Prognostic Factors. Clin Med Insights Oncol 2017; 11:1179554917731072. [PMID: 28989291 PMCID: PMC5624347 DOI: 10.1177/1179554917731072] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2017] [Accepted: 06/20/2017] [Indexed: 02/04/2023] Open
Abstract
Hodgkin lymphoma is a highly curable malignancy in early and advanced stages. Most patients are diagnosed in their teens or twenties and are expected to live decades beyond their treatment. Therefore, the toxicity of treatment must be balanced with the goal of cure. Thus, treatment has been refined through prognostic models and positron emission tomography-computed tomography (PET-CT)-directed therapy. Stratification by prognostic models defines groups of patients with favorable characteristics who may be treated with less intensive therapy upfront, including fewer cycles of chemotherapy, lower doses of radiation, or omission of radiation altogether. Alternatively, high-risk patients may be assigned to a more aggressive initial approach. The modern use of interim PET-CT allows further tailoring of treatment by response.
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Affiliation(s)
- Pamela B Allen
- Robert H. Lurie Comprehensive Cancer Center and Division of Hematology and Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Leo I Gordon
- Department of Hematology and Medical Oncology, Emory University Winship Cancer Institute, Atlanta, GA, USA
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15
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Bond DA, Alinari L. Emerging treatment options for the management of Hodgkin's lymphoma: clinical utility of nivolumab. J Blood Med 2017; 8:41-54. [PMID: 28546779 PMCID: PMC5436782 DOI: 10.2147/jbm.s117452] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Classical Hodgkin's lymphoma (cHL) is a B-cell malignancy comprised of pathologic Reed Sternberg cells with a surrounding immune-tolerant inflammatory milieu. RS cells evade immune recognition in part through programmed death ligand 1 (PD-L1) overexpression, which is genetically programmed through copy number alterations, polysomy, and amplification of the 9p24.1 locus encoding PD-L1. By engaging with PD-1+ T-cells, PD-L1 delivers a potent immune suppressive signal promoting immunologic escape of the tumor cell. Enhancing antitumor immune response by targeting PD-1 with the monoclonal antibody nivolumab has proved to be effective in multiple solid tumors, but the highest response rates to date have been reported in patients with cHL, with over 65% of treated patients achieving an objective clinical response. In this review, we will summarize the published evidence regarding the activity of nivolumab in cHL as well as its current place in therapy. We will review the pharmacology, mechanism of action, and side effects of nivolumab as well as the emerging data indicating possible increased risk of graft versus host disease in patients treated with PD-1 inhibitors either pre- or post-allogeneic stem cell transplant. Given the remarkable single-agent activity and safety profile of PD-1 inhibitors in heavily pretreated patients with cHL, the possibility of employing nivolumab in combination with other active agents and earlier in therapy is a promising area of active investigation, and we will briefly summarize current clinical trials.
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Affiliation(s)
- David A Bond
- Department of Internal Medicine, Division of Hematology, Arthur G James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Lapo Alinari
- Department of Internal Medicine, Division of Hematology, Arthur G James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA
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16
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Leslie LA, Skarbnik AP, Bejot C, Stives S, Feldman TA, Goy AH. Targeting indolent non-Hodgkin lymphoma. Expert Rev Hematol 2017; 10:299-313. [PMID: 28277849 DOI: 10.1080/17474086.2017.1303374] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
INTRODUCTION Due to recent advancements in the understanding of the molecular pathogenesis of B-cell malignancies, there has been an explosion of innovative agents in development. The purpose of this review is to efficiently summarize novel therapies with activity in indolent non-Hodgkin lymphoma (iNHL) targeting surface antigens, signaling pathways, and the tumor microenvironment. Areas covered: A literature search was performed to identify preclinical data and clinical trials focused on the use of targeted therapies in iNHL subtypes including follicular lymphoma, marginal zone lymphoma, small lymphocytic lymphoma, and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia. Classes reviewed include monoclonal antibodies, antibody-drug conjugates, immunomodulatory agents, B-cell receptor pathway inhibitors, Bcl-2 inhibitors, checkpoint inhibitors, chromatin and epigenetic modulating agents, and CAR T-cells. Expert commentary: Opinions regarding strategies to address the prioritization of novel agents entering clinical development, the determination of rational combination therapy, the development of novel endpoints to expedite clinical development, and the movement towards novel consolidative approaches with immuno- and cellular therapy in an attempt to provide curative treatment options are provided. Also, the economic impact of indefinite therapy is discussed.
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Affiliation(s)
- Lori A Leslie
- a Lymphoma Division , John Theurer Cancer Center , Hackensack , NJ , USA
| | - Alan P Skarbnik
- a Lymphoma Division , John Theurer Cancer Center , Hackensack , NJ , USA
| | - Coleen Bejot
- a Lymphoma Division , John Theurer Cancer Center , Hackensack , NJ , USA
| | - Susan Stives
- a Lymphoma Division , John Theurer Cancer Center , Hackensack , NJ , USA
| | - Tatyana A Feldman
- a Lymphoma Division , John Theurer Cancer Center , Hackensack , NJ , USA
| | - Andre H Goy
- a Lymphoma Division , John Theurer Cancer Center , Hackensack , NJ , USA
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17
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Wray J, Flampouri S, Slayton W, Joyce M, Sandler E, Morris CG, Li Z, Indelicato DJ, Mendenhall NP, Hoppe BS. Proton Therapy for Pediatric Hodgkin Lymphoma. Pediatr Blood Cancer 2016; 63:1522-6. [PMID: 27149120 DOI: 10.1002/pbc.26044] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2015] [Accepted: 03/24/2016] [Indexed: 01/11/2023]
Abstract
BACKGROUND Compared to X-ray radiation therapy, proton therapy (PT) reduces the radiation dose to organs at risk, which is expected to translate into fewer second cancers and less cardiac morbidity decades after treatment. The Children's Oncology Group high-risk pediatric Hodgkin lymphoma (PHL) protocol, AHOD1331, allows the use of PT, yet limited data exist on the use of PT in PHL. PROCEDURE Between 2010 and 2014, 22 pediatric patients were treated with PT for PHL at our institution: 7 intermediate-risk patients, 11 high-risk patients, and 4 relapsed patients. The patients' age ranged from 6 to 18 years old. Median follow-up was 36 months. All patients received chemotherapy before PT. RESULTS The 2-year and 3-year overall survival rates were both 94%, and the progression-free survival rate was 86%. Recurrences occurred in three high-risk patients: one isolated in-field cervical lymph node and two in-field and out-of-field. All recurrences occurred within 5 months of completing PT. No PT-related grade 3 or higher acute or late complications were observed. CONCLUSION PT for PHL showed no short-term severe toxicity and yields similar short-term control to recently published large multi-institutional clinical trials.
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Affiliation(s)
- Justin Wray
- Department of Radiation Oncology, University of Florida, Gainesville, Florida.,University of Florida Health Proton Therapy Institute, Jacksonville, Florida
| | - Stella Flampouri
- Department of Radiation Oncology, University of Florida, Gainesville, Florida.,University of Florida Health Proton Therapy Institute, Jacksonville, Florida
| | - William Slayton
- Division of Hematology and Oncology, University of Florida Department of Pediatrics, Gainesville, Florida
| | - Michael Joyce
- Division of Hematology and Oncology, Department of Pediatrics, Nemours Children's Clinic, Jacksonville, Florida
| | - Eric Sandler
- Division of Hematology and Oncology, Department of Pediatrics, Nemours Children's Clinic, Jacksonville, Florida
| | - Christopher G Morris
- Department of Radiation Oncology, University of Florida, Gainesville, Florida.,University of Florida Health Proton Therapy Institute, Jacksonville, Florida
| | - Zuofeng Li
- University of Florida Health Proton Therapy Institute, Jacksonville, Florida
| | - Daniel J Indelicato
- University of Florida Health Proton Therapy Institute, Jacksonville, Florida
| | - Nancy P Mendenhall
- Department of Radiation Oncology, University of Florida, Gainesville, Florida.,University of Florida Health Proton Therapy Institute, Jacksonville, Florida
| | - Bradford S Hoppe
- Department of Radiation Oncology, University of Florida, Gainesville, Florida.,University of Florida Health Proton Therapy Institute, Jacksonville, Florida
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18
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ACR Appropriateness Criteria® Hodgkin Lymphoma—Unfavorable Clinical Stage I and II. Am J Clin Oncol 2016; 39:384-95. [DOI: 10.1097/coc.0000000000000294] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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19
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Brentuximab vedotin and AVD followed by involved-site radiotherapy in early stage, unfavorable risk Hodgkin lymphoma. Blood 2016; 128:1458-64. [PMID: 27458003 DOI: 10.1182/blood-2016-03-703470] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Accepted: 07/05/2016] [Indexed: 11/20/2022] Open
Abstract
This multicenter pilot study assessed the safety and efficacy of brentuximab vedotin (BV) and AVD (adriamycin, vinblastine, and dacarbazine) followed by 30 Gy involved site radiation therapy (ISRT). Patients with newly diagnosed, early stage classical Hodgkin lymphoma (HL) with unfavorable-risk features were treated with 4 cycles of BV and AVD. Patients who achieved a negative positron emission tomography (PET) scan (Deauville score of 1-3) received 30 Gy ISRT. Thirty patients received treatment and were assessable for toxicity. Twenty-nine patients completed 4 cycles of BV + AVD, and 25 patients BV + AVD + 30 Gy ISRT. No clinically significant noninfectious pneumonitis was observed. Serious adverse events (≥grade 3) were reported in 4 patients, including febrile neutropenia, peripheral neuropathy, and hypertension. After 2 and 4 cycles of BV + AVD, 90% (26 of 29) and 93% (27 or 29) of patients achieved a negative PET scan, respectively. Two patients with biopsy-proven primary refractory HL were treated off-study. All 25 patients who completed BV + AVD + ISRT achieved a complete response. With a median follow-up of 18.8 months, by intent to treat, the 1-year progression-free survival is 93.3% (95% confidence interval, 84-102). Overall, the treatment was well-tolerated with no evidence of significant pulmonary toxicity. The majority of patients (≥90%) achieved negative interim PET scans after 2 and 4 cycles of BV + AVD. Excluding the 2 primary refractory patients, all patients are disease free, suggesting that this is a highly active treatment program even in patients with substantial disease bulk. This trial was registered at www.clinicaltrials.gov as #NCT01868451.
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20
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Effect of chemotherapy alone with adult chemotherapy regimens on prognosis of children and adolescents with Hodgkin's disease. Jpn J Clin Oncol 2016; 46:667-73. [DOI: 10.1093/jjco/hyw051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Accepted: 03/27/2016] [Indexed: 11/14/2022] Open
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21
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Hodgkin Lymphoma: the Changing Role of Radiation Therapy in Early-Stage Disease—the Role of Functional Imaging. Curr Treat Options Oncol 2016; 16:45. [PMID: 26187795 DOI: 10.1007/s11864-015-0360-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Early-stage classical Hodgkin lymphoma (CHL) is a highly curable malignancy. Historically, extended-field radiotherapy (EFRT) alone showed excellent cure rates, but the risk of radiotherapy (RT)-associated toxicities led to combined modality therapy (CMT) replacing RT alone. RT has subsequently evolved further with significant reductions of dose and field size, and is currently restricted to involved sites only (ISRT). Contemporary CMT yields cure rates in excess of 85%, and most studies do not have adequate follow-up required to evaluate the risk reduction in late effects. In an effort to avoid RT altogether, response-adapted treatment approaches utilizing results of interim [(18)F]fluorodeoxyglucose (FDG) positron emission tomography with fused computed tomography (PET/CT) imaging have been studied. Results from two studies in favorable-risk (UK RAPID and EORTC H10F) and one in unfavorable-risk patients (EORTC H10U) suggest that omission of RT in patients with a negative interim PET/CT response (Deauville score ≤2) yields slightly inferior progression-free survival (PFS) compared to conventional CMT, but with no difference in overall survival (OS) albeit with short-term follow-up. In order to extrapolate results to daily practice, it is critical to understand the selection of patients entered on trials since definitions of favorable and unfavorable disease vary between study groups. Currently, CMT continues to be the standard of care for the vast majority of patients with early-stage CHL and RT is an integral part of therapy in patients with bulky disease. However, for selected patients with favorable characteristics, emerging data suggest that a chemotherapy-alone approach is reasonable.
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22
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Batson S, Greenall G, Hudson P. Review of the Reporting of Survival Analyses within Randomised Controlled Trials and the Implications for Meta-Analysis. PLoS One 2016; 11:e0154870. [PMID: 27149107 PMCID: PMC4858202 DOI: 10.1371/journal.pone.0154870] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2015] [Accepted: 04/20/2016] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Meta-analysis is a growing approach to evidence synthesis and network meta-analysis in particular represents an important and developing method within Health Technology Assessment (HTA). Meta-analysis of survival data is usually performed using the individual summary statistic-the hazard ratio (HR) from each randomised controlled trial (RCT). OBJECTIVES The objectives of this study are to: (i) review the methods and reporting of survival analyses in oncology RCTs; and (ii) assess the suitability and relevance of survival data reported in RCTs for inclusion into meta-analysis. METHODS Five oncology journals were searched to identify Phase III RCTs published between April and July 2015. Eligible studies included those that analysed a survival outcome. RESULTS Thirty-two RCTs reporting survival outcomes in cancer populations were identified. None of the publications reported details relating to a strategy for statistical model building, the goodness of fit of the final model, or final model validation for the analysis of survival outcomes. The majority of studies (88%) reported the use of Cox proportional hazards (PH) regression to analyse survival endpoints. However, most publications failed to report the validation of the statistical models in terms of the PH assumption. CONCLUSIONS This review highlights deficiencies in terms of reporting the methods and validity of survival analyses within oncology RCTs. We support previous recommendations to encourage authors to improve the reporting of survival analyses in journal publications. We also recommend that the final choice of a statistical model for survival should be informed by goodness of model fit to a given dataset, and that model assumptions are validated. The failure of trial investigators and statisticians to investigate the PH for RCT survival data is likely to result in clinical decisions based on inappropriate methods. The development of alternative approaches for the meta-analysis of survival outcomes when the PH assumption is implausible is required if valid clinical decisions are to be made.
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23
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Roemer MGM, Advani RH, Ligon AH, Natkunam Y, Redd RA, Homer H, Connelly CF, Sun HH, Daadi SE, Freeman GJ, Armand P, Chapuy B, de Jong D, Hoppe RT, Neuberg DS, Rodig SJ, Shipp MA. PD-L1 and PD-L2 Genetic Alterations Define Classical Hodgkin Lymphoma and Predict Outcome. J Clin Oncol 2016; 34:2690-7. [PMID: 27069084 DOI: 10.1200/jco.2016.66.4482] [Citation(s) in RCA: 603] [Impact Index Per Article: 67.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
PURPOSE Classical Hodgkin lymphomas (cHLs) include small numbers of malignant Reed-Sternberg cells within an extensive but ineffective inflammatory/immune cell infiltrate. In cHL, chromosome 9p24.1/PD-L1/PD-L2 alterations increase the abundance of the PD-1 ligands, PD-L1 and PD-L2, and their further induction through Janus kinase 2-signal transducers and activators of transcription signaling. The unique composition of cHL limits its analysis with high-throughput genomic assays. Therefore, the precise incidence, nature, and prognostic significance of PD-L1/PD-L2 alterations in cHL remain undefined. METHODS We used a fluorescent in situ hybridization assay to evaluate CD274/PD-L1 and PDCD1LG2/PD-L2 alterations in 108 biopsy specimens from patients with newly diagnosed cHL who were treated with the Stanford V regimen and had long-term follow-up. In each case, the frequency and magnitude of 9p24.1 alterations-polysomy, copy gain, and amplification-were determined, and the expression of PD-L1 and PD-L2 was evaluated by immunohistochemistry. We also assessed the association of 9p24.1 alterations with clinical parameters, which included stage (early stage I/II favorable risk, early stage unfavorable risk, advanced stage [AS] III/IV) and progression-free survival (PFS). RESULTS Ninety-seven percent of all evaluated cHLs had concordant alterations of the PD-L1 and PD-L2 loci (polysomy, 5% [five of 108]; copy gain, 56% [61 of 108]; amplification, 36% [39 of 108]). There was an association between PD-L1 protein expression and relative genetic alterations in this series. PFS was significantly shorter for patients with 9p24.1 amplification, and the incidence of 9p24.1 amplification was increased in patients with AS cHL. CONCLUSION PD-L1/PD-L2 alterations are a defining feature of cHL. Amplification of 9p24.1 is more common in patients with AS disease and associated with shorter PFS in this series. Further analyses of 9p24.1 alterations in patients treated with standard cHL induction regimens or checkpoint blockade are warranted.
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Affiliation(s)
- Margaretha G M Roemer
- Margaretha G.M. Roemer, Robert A. Redd, Heather Homer, Courtney F. Connelly, Gordon J. Freeman, Philippe Armand, Bjoern Chapuy, Donna S. Neuberg, and Margaret A. Shipp, Dana-Farber Cancer Institute; Azra H. Ligon, Heather H. Sun, and Scott J. Rodig, Brigham and Women's Hospital, Boston, MA; Margaretha G.M. Roemer and Daphne de Jong, VU University Medical Center, Amsterdam, the Netherlands; and Ranjana H. Advani, Yasodha Natkunam, Sarah E. Daadi, and Richard T. Hoppe, Stanford University Medical Center, Stanford, CA
| | - Ranjana H Advani
- Margaretha G.M. Roemer, Robert A. Redd, Heather Homer, Courtney F. Connelly, Gordon J. Freeman, Philippe Armand, Bjoern Chapuy, Donna S. Neuberg, and Margaret A. Shipp, Dana-Farber Cancer Institute; Azra H. Ligon, Heather H. Sun, and Scott J. Rodig, Brigham and Women's Hospital, Boston, MA; Margaretha G.M. Roemer and Daphne de Jong, VU University Medical Center, Amsterdam, the Netherlands; and Ranjana H. Advani, Yasodha Natkunam, Sarah E. Daadi, and Richard T. Hoppe, Stanford University Medical Center, Stanford, CA
| | - Azra H Ligon
- Margaretha G.M. Roemer, Robert A. Redd, Heather Homer, Courtney F. Connelly, Gordon J. Freeman, Philippe Armand, Bjoern Chapuy, Donna S. Neuberg, and Margaret A. Shipp, Dana-Farber Cancer Institute; Azra H. Ligon, Heather H. Sun, and Scott J. Rodig, Brigham and Women's Hospital, Boston, MA; Margaretha G.M. Roemer and Daphne de Jong, VU University Medical Center, Amsterdam, the Netherlands; and Ranjana H. Advani, Yasodha Natkunam, Sarah E. Daadi, and Richard T. Hoppe, Stanford University Medical Center, Stanford, CA
| | - Yasodha Natkunam
- Margaretha G.M. Roemer, Robert A. Redd, Heather Homer, Courtney F. Connelly, Gordon J. Freeman, Philippe Armand, Bjoern Chapuy, Donna S. Neuberg, and Margaret A. Shipp, Dana-Farber Cancer Institute; Azra H. Ligon, Heather H. Sun, and Scott J. Rodig, Brigham and Women's Hospital, Boston, MA; Margaretha G.M. Roemer and Daphne de Jong, VU University Medical Center, Amsterdam, the Netherlands; and Ranjana H. Advani, Yasodha Natkunam, Sarah E. Daadi, and Richard T. Hoppe, Stanford University Medical Center, Stanford, CA
| | - Robert A Redd
- Margaretha G.M. Roemer, Robert A. Redd, Heather Homer, Courtney F. Connelly, Gordon J. Freeman, Philippe Armand, Bjoern Chapuy, Donna S. Neuberg, and Margaret A. Shipp, Dana-Farber Cancer Institute; Azra H. Ligon, Heather H. Sun, and Scott J. Rodig, Brigham and Women's Hospital, Boston, MA; Margaretha G.M. Roemer and Daphne de Jong, VU University Medical Center, Amsterdam, the Netherlands; and Ranjana H. Advani, Yasodha Natkunam, Sarah E. Daadi, and Richard T. Hoppe, Stanford University Medical Center, Stanford, CA
| | - Heather Homer
- Margaretha G.M. Roemer, Robert A. Redd, Heather Homer, Courtney F. Connelly, Gordon J. Freeman, Philippe Armand, Bjoern Chapuy, Donna S. Neuberg, and Margaret A. Shipp, Dana-Farber Cancer Institute; Azra H. Ligon, Heather H. Sun, and Scott J. Rodig, Brigham and Women's Hospital, Boston, MA; Margaretha G.M. Roemer and Daphne de Jong, VU University Medical Center, Amsterdam, the Netherlands; and Ranjana H. Advani, Yasodha Natkunam, Sarah E. Daadi, and Richard T. Hoppe, Stanford University Medical Center, Stanford, CA
| | - Courtney F Connelly
- Margaretha G.M. Roemer, Robert A. Redd, Heather Homer, Courtney F. Connelly, Gordon J. Freeman, Philippe Armand, Bjoern Chapuy, Donna S. Neuberg, and Margaret A. Shipp, Dana-Farber Cancer Institute; Azra H. Ligon, Heather H. Sun, and Scott J. Rodig, Brigham and Women's Hospital, Boston, MA; Margaretha G.M. Roemer and Daphne de Jong, VU University Medical Center, Amsterdam, the Netherlands; and Ranjana H. Advani, Yasodha Natkunam, Sarah E. Daadi, and Richard T. Hoppe, Stanford University Medical Center, Stanford, CA
| | - Heather H Sun
- Margaretha G.M. Roemer, Robert A. Redd, Heather Homer, Courtney F. Connelly, Gordon J. Freeman, Philippe Armand, Bjoern Chapuy, Donna S. Neuberg, and Margaret A. Shipp, Dana-Farber Cancer Institute; Azra H. Ligon, Heather H. Sun, and Scott J. Rodig, Brigham and Women's Hospital, Boston, MA; Margaretha G.M. Roemer and Daphne de Jong, VU University Medical Center, Amsterdam, the Netherlands; and Ranjana H. Advani, Yasodha Natkunam, Sarah E. Daadi, and Richard T. Hoppe, Stanford University Medical Center, Stanford, CA
| | - Sarah E Daadi
- Margaretha G.M. Roemer, Robert A. Redd, Heather Homer, Courtney F. Connelly, Gordon J. Freeman, Philippe Armand, Bjoern Chapuy, Donna S. Neuberg, and Margaret A. Shipp, Dana-Farber Cancer Institute; Azra H. Ligon, Heather H. Sun, and Scott J. Rodig, Brigham and Women's Hospital, Boston, MA; Margaretha G.M. Roemer and Daphne de Jong, VU University Medical Center, Amsterdam, the Netherlands; and Ranjana H. Advani, Yasodha Natkunam, Sarah E. Daadi, and Richard T. Hoppe, Stanford University Medical Center, Stanford, CA
| | - Gordon J Freeman
- Margaretha G.M. Roemer, Robert A. Redd, Heather Homer, Courtney F. Connelly, Gordon J. Freeman, Philippe Armand, Bjoern Chapuy, Donna S. Neuberg, and Margaret A. Shipp, Dana-Farber Cancer Institute; Azra H. Ligon, Heather H. Sun, and Scott J. Rodig, Brigham and Women's Hospital, Boston, MA; Margaretha G.M. Roemer and Daphne de Jong, VU University Medical Center, Amsterdam, the Netherlands; and Ranjana H. Advani, Yasodha Natkunam, Sarah E. Daadi, and Richard T. Hoppe, Stanford University Medical Center, Stanford, CA
| | - Philippe Armand
- Margaretha G.M. Roemer, Robert A. Redd, Heather Homer, Courtney F. Connelly, Gordon J. Freeman, Philippe Armand, Bjoern Chapuy, Donna S. Neuberg, and Margaret A. Shipp, Dana-Farber Cancer Institute; Azra H. Ligon, Heather H. Sun, and Scott J. Rodig, Brigham and Women's Hospital, Boston, MA; Margaretha G.M. Roemer and Daphne de Jong, VU University Medical Center, Amsterdam, the Netherlands; and Ranjana H. Advani, Yasodha Natkunam, Sarah E. Daadi, and Richard T. Hoppe, Stanford University Medical Center, Stanford, CA
| | - Bjoern Chapuy
- Margaretha G.M. Roemer, Robert A. Redd, Heather Homer, Courtney F. Connelly, Gordon J. Freeman, Philippe Armand, Bjoern Chapuy, Donna S. Neuberg, and Margaret A. Shipp, Dana-Farber Cancer Institute; Azra H. Ligon, Heather H. Sun, and Scott J. Rodig, Brigham and Women's Hospital, Boston, MA; Margaretha G.M. Roemer and Daphne de Jong, VU University Medical Center, Amsterdam, the Netherlands; and Ranjana H. Advani, Yasodha Natkunam, Sarah E. Daadi, and Richard T. Hoppe, Stanford University Medical Center, Stanford, CA
| | - Daphne de Jong
- Margaretha G.M. Roemer, Robert A. Redd, Heather Homer, Courtney F. Connelly, Gordon J. Freeman, Philippe Armand, Bjoern Chapuy, Donna S. Neuberg, and Margaret A. Shipp, Dana-Farber Cancer Institute; Azra H. Ligon, Heather H. Sun, and Scott J. Rodig, Brigham and Women's Hospital, Boston, MA; Margaretha G.M. Roemer and Daphne de Jong, VU University Medical Center, Amsterdam, the Netherlands; and Ranjana H. Advani, Yasodha Natkunam, Sarah E. Daadi, and Richard T. Hoppe, Stanford University Medical Center, Stanford, CA
| | - Richard T Hoppe
- Margaretha G.M. Roemer, Robert A. Redd, Heather Homer, Courtney F. Connelly, Gordon J. Freeman, Philippe Armand, Bjoern Chapuy, Donna S. Neuberg, and Margaret A. Shipp, Dana-Farber Cancer Institute; Azra H. Ligon, Heather H. Sun, and Scott J. Rodig, Brigham and Women's Hospital, Boston, MA; Margaretha G.M. Roemer and Daphne de Jong, VU University Medical Center, Amsterdam, the Netherlands; and Ranjana H. Advani, Yasodha Natkunam, Sarah E. Daadi, and Richard T. Hoppe, Stanford University Medical Center, Stanford, CA
| | - Donna S Neuberg
- Margaretha G.M. Roemer, Robert A. Redd, Heather Homer, Courtney F. Connelly, Gordon J. Freeman, Philippe Armand, Bjoern Chapuy, Donna S. Neuberg, and Margaret A. Shipp, Dana-Farber Cancer Institute; Azra H. Ligon, Heather H. Sun, and Scott J. Rodig, Brigham and Women's Hospital, Boston, MA; Margaretha G.M. Roemer and Daphne de Jong, VU University Medical Center, Amsterdam, the Netherlands; and Ranjana H. Advani, Yasodha Natkunam, Sarah E. Daadi, and Richard T. Hoppe, Stanford University Medical Center, Stanford, CA
| | - Scott J Rodig
- Margaretha G.M. Roemer, Robert A. Redd, Heather Homer, Courtney F. Connelly, Gordon J. Freeman, Philippe Armand, Bjoern Chapuy, Donna S. Neuberg, and Margaret A. Shipp, Dana-Farber Cancer Institute; Azra H. Ligon, Heather H. Sun, and Scott J. Rodig, Brigham and Women's Hospital, Boston, MA; Margaretha G.M. Roemer and Daphne de Jong, VU University Medical Center, Amsterdam, the Netherlands; and Ranjana H. Advani, Yasodha Natkunam, Sarah E. Daadi, and Richard T. Hoppe, Stanford University Medical Center, Stanford, CA
| | - Margaret A Shipp
- Margaretha G.M. Roemer, Robert A. Redd, Heather Homer, Courtney F. Connelly, Gordon J. Freeman, Philippe Armand, Bjoern Chapuy, Donna S. Neuberg, and Margaret A. Shipp, Dana-Farber Cancer Institute; Azra H. Ligon, Heather H. Sun, and Scott J. Rodig, Brigham and Women's Hospital, Boston, MA; Margaretha G.M. Roemer and Daphne de Jong, VU University Medical Center, Amsterdam, the Netherlands; and Ranjana H. Advani, Yasodha Natkunam, Sarah E. Daadi, and Richard T. Hoppe, Stanford University Medical Center, Stanford, CA.
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