Michael MacManus1, Richard Fisher1, Daniel Roos1, Peter O'Brien1, Andrew Macann1, Sidney Davis1, Richard Tsang1, David Christie1, Bev McClure1, David Joseph1, Jayasingham Jayamohan1, John F Seymour1. 1. Michael MacManus, Richard Fisher, Bev McClure, and John F. Seymour, Peter MacCallum Cancer Centre; Michael MacManus and John F. Seymour, University of Melbourne; Melbourne; Sidney Davis, The Alfred Hospital, Prahran, Victoria; Daniel Roos, The Royal Adelaide Hospital and The University of Adelaide, Adelaide, South Australia; Peter O'Brien, Genesis Cancer Care, Newcastle; Jayasingham Jayamohan, Westmead Hospital, Sydney, New South Wales; David Christie, Genesis Cancer Care, Tugun, Queensland; David Joseph, Sir Charles Gairdner Hospital Perth, Perth, Western Australia, Austrailia; Andrew Macann, Auckland City Hospital, Auckland, New Zealand; and Richard Tsang, Princess Margaret Hospital, Toronto, Ontario, Canada.
Abstract
PURPOSE: Follicular lymphoma (FL) is curable by involved-field radiotherapy (IFRT) in < 50% of patients with stage I to II disease. We hypothesized that adding systemic therapy to IFRT would improve long-term progression-free survival (PFS). PATIENTS AND METHODS: A multicenter randomized controlled trial enrolled patients with stage I to II low-grade FL after staging computed tomography scans and bone marrow biopsies. 18F-labeled fluorodeoxyglucose-positron emission tomography (PET) was not mandatory. Patients were randomly assigned to either arm A (30 Gy IFRT alone) or arm B (IFRT plus six cycles of cyclophosphamide, vincristine, and prednisolone [CVP]). From 2006, rituximab was added to arm B (R-CVP). RESULTS:Between 2000 and 2012, 150 patients were enrolled, 75 per arm. In arm B, 44 patients were allocated to receiveCVP and 31 were allocated to receive R-CVP. At randomization, 75% had stage I, the median age was 57 years, 52% were male, and 48% were PET staged. With a median follow-up of 9.6 years (range, 3.1 to 15.8 years), PFS was superior in arm B (hazard ratio, 0.57; 95% CI, 0.34 to 0.95; P = .033). Ten-year PFS rates were 59% (95% CI, 46% to 74%) and 41% (95% CI, 30% to 57%) for arms B and A, respectively. Patients in arm B who received R-CVP had markedly superior PFS compared with contemporaneous patients in arm A (hazard ratio, 0.26; 95% CI, 0.07 to 0.97; P = .045). Fewer involved regions ( P = .047) and PET staging ( P = .056) were associated with better PFS. Histologic transformation occurred in four and 10 patients in arms B and A, respectively ( P = .1). Ten deaths occurred in arm A versus five in arm B, but overall survival was not significantly different ( P = .40; 87% and 95% at 10 years, respectively). CONCLUSION:Systemic therapy with R-CVP after IFRT reduced relapse outside radiation fields and significantly improved PFS. IFRT followed by immunochemotherapy is more effective than IFRT in early-stage FL.
RCT Entities:
PURPOSE:Follicular lymphoma (FL) is curable by involved-field radiotherapy (IFRT) in < 50% of patients with stage I to II disease. We hypothesized that adding systemic therapy to IFRT would improve long-term progression-free survival (PFS). PATIENTS AND METHODS: A multicenter randomized controlled trial enrolled patients with stage I to II low-grade FL after staging computed tomography scans and bone marrow biopsies. 18F-labeled fluorodeoxyglucose-positron emission tomography (PET) was not mandatory. Patients were randomly assigned to either arm A (30 Gy IFRT alone) or arm B (IFRT plus six cycles of cyclophosphamide, vincristine, and prednisolone [CVP]). From 2006, rituximab was added to arm B (R-CVP). RESULTS: Between 2000 and 2012, 150 patients were enrolled, 75 per arm. In arm B, 44 patients were allocated to receive CVP and 31 were allocated to receive R-CVP. At randomization, 75% had stage I, the median age was 57 years, 52% were male, and 48% were PET staged. With a median follow-up of 9.6 years (range, 3.1 to 15.8 years), PFS was superior in arm B (hazard ratio, 0.57; 95% CI, 0.34 to 0.95; P = .033). Ten-year PFS rates were 59% (95% CI, 46% to 74%) and 41% (95% CI, 30% to 57%) for arms B and A, respectively. Patients in arm B who received R-CVP had markedly superior PFS compared with contemporaneous patients in arm A (hazard ratio, 0.26; 95% CI, 0.07 to 0.97; P = .045). Fewer involved regions ( P = .047) and PET staging ( P = .056) were associated with better PFS. Histologic transformation occurred in four and 10 patients in arms B and A, respectively ( P = .1). Ten deaths occurred in arm A versus five in arm B, but overall survival was not significantly different ( P = .40; 87% and 95% at 10 years, respectively). CONCLUSION: Systemic therapy with R-CVP after IFRT reduced relapse outside radiation fields and significantly improved PFS. IFRT followed by immunochemotherapy is more effective than IFRT in early-stage FL.
Authors: Michael S Binkley; Jessica L Brady; Carla Hajj; Monica Chelius; Karen Chau; Alex Balogh; Mario Levis; Andrea Riccardo Filippi; Michael Jones; Sameera Ahmed; Michael MacManus; Andrew Wirth; Masahiko Oguchi; Anders Krog Vistisen; Therese Youssef Andraos; Andrea K Ng; Berthe M P Aleman; Seo Hee Choi; Youlia M Kirova; Sara Hardy; Gabriele Reinartz; Hans T Eich; Scott V Bratman; Louis S Constine; Chang-Ok Suh; Bouthaina Dabaja; Tarec C El-Galaly; David C Hodgson; Umberto Ricardi; Joachim Yahalom; N George Mikhaeel; Richard T Hoppe Journal: Int J Radiat Oncol Biol Phys Date: 2019-03-08 Impact factor: 7.038
Authors: Joshua W D Tobin; Gabrielle Rule; Katherine Colvin; Lourdes Calvente; David Hodgson; Stephen Bell; Chengetai Dunduru; James Gallo; Erica S Tsang; Xuan Tan; Jonathan Wong; Jessica Pearce; Robert Campbell; Shao Tneh; Sophie Shorten; Melissa Ng; Tara Cochrane; Constantine S Tam; Emad Abro; Eliza Hawkes; Georgina Hodges; Roopesh Kansara; Dipti Talaulikar; Michael Gilbertson; Anna M Johnston; Kerry J Savage; Diego Villa; Kirk Morris; Sumi Ratnasingam; Wojt Janowski; Robert Kridel; Chan Y Cheah; Michael MacManus; Nicholas Matigian; Peter Mollee; Maher K Gandhi; Greg Hapgood Journal: Blood Adv Date: 2019-10-08
Authors: Anna Zoellner; Klaus Herfarth; Michael Herold; Wolfram Klapper; Nicole Skoetz; Wolfgang Hiddemann Journal: Dtsch Arztebl Int Date: 2021-04-30 Impact factor: 8.251
Authors: Michael P MacManus; Rodney J Hicks; Mathias Bressel; Belinda A Campbell; Andrew Wirth; Gail Ryan; H Miles Prince; Max Wolf; Rachel Brown; John F Seymour Journal: Cancers (Basel) Date: 2020-04-17 Impact factor: 6.639
Authors: Klaus Herfarth; Peter Borchmann; Sven Schnaidt; Karin Hohloch; Volker Budach; Marianne Engelhard; Andreas Viardot; Rita Engenhart-Cabillic; Ulrich Keller; Gabriele Reinartz; Hans-Theodor Eich; Mathias Witzens-Harig; Clemens F Hess; Bernd Dörken; Jan Dürig; Thomas Wiegel; Wolfgang Hiddemann; Eva Hoster; Christiane Pott; Martin Dreyling Journal: Hemasphere Date: 2018-11-30
Authors: Constantin Lapa; Ursula Nestle; Nathalie L Albert; Christian Baues; Ambros Beer; Andreas Buck; Volker Budach; Rebecca Bütof; Stephanie E Combs; Thorsten Derlin; Matthias Eiber; Wolfgang P Fendler; Christian Furth; Cihan Gani; Eleni Gkika; Anca-L Grosu; Christoph Henkenberens; Harun Ilhan; Steffen Löck; Simone Marnitz-Schulze; Matthias Miederer; Michael Mix; Nils H Nicolay; Maximilian Niyazi; Christoph Pöttgen; Claus M Rödel; Imke Schatka; Sarah M Schwarzenboeck; Andrei S Todica; Wolfgang Weber; Simone Wegen; Thomas Wiegel; Constantinos Zamboglou; Daniel Zips; Klaus Zöphel; Sebastian Zschaeck; Daniela Thorwarth; Esther G C Troost Journal: Strahlenther Onkol Date: 2021-07-14 Impact factor: 3.621