BACKGROUND: We tested interim positron-emission tomography-computed tomography (PET-CT) as a measure of early response to chemotherapy in order to guide treatment for patients with advanced Hodgkin's lymphoma. METHODS: Patients with newly diagnosed advanced classic Hodgkin's lymphoma underwent a baseline PETCT scan, received two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy, and then underwent an interim PET-CT scan. Images were centrally reviewed with the use of a 5-point scale for PET findings. Patients with negative PET findings after two cycles were randomly assigned to continue ABVD (ABVD group) or omit bleomycin (AVD group) in cycles 3 through 6. Those with positive PET findings after two cycles received BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone). Radiotherapy was not recommended for patients with negative findings on interim scans. The primary outcome was the difference in the 3-year progression-free survival rate between randomized groups, a noninferiority comparison to exclude a difference of 5 or more percentage points. RESULTS: A total of 1214 patients were registered; 937 of the 1119 patients (83.7%) who underwent an interim PET-CT scan according to protocol had negative findings. With a median follow-up of 41 months, the 3-year progression-free survival rate and overall survival rate in the ABVD group were 85.7% (95% confidence interval [CI], 82.1 to 88.6) and 97.2% (95% CI, 95.1 to 98.4), respectively; the corresponding rates in the AVD group were 84.4% (95% CI, 80.7 to 87.5) and 97.6% (95% CI, 95.6 to 98.7). The absolute difference in the 3-year progression-free survival rate (ABVD minus AVD) was 1.6 percentage points (95% CI, -3.2 to 5.3). Respiratory adverse events were more severe in the ABVD group than in the AVD group. BEACOPP was given to the 172 patients with positive findings on the interim scan, and 74.4% had negative findings on a third PET-CT scan; the 3-year progression-free survival rate was 67.5% and the overall survival rate 87.8%. A total of 62 patients died during the trial (24 from Hodgkin's lymphoma), for a 3-year progression-free survival rate of 82.6% and an overall survival rate of 95.8%. CONCLUSIONS: Although the results fall just short of the specified noninferiority margin, the omission of bleomycin from the ABVD regimen after negative findings on interim PET resulted in a lower incidence of pulmonary toxic effects than with continued ABVD but not significantly lower efficacy.

Adapted treatment guided by interim PET-CT scan in advanced Hodgkin's lymphoma / Johnson, Peter; Federico, Massimo; Kirkwood, Amy; Fosså, Alexander; Berkahn, Leanne; Carella, Angelo; D'Amore, Francesco; Enblad, Gunilla; Franceschetto, Antonella; Fulham, Michael; Luminari, Stefano; O'Doherty, Michael; Patrick, Pip; Roberts, Thomas; Sidra, Gamal; Stevens, Lindsey; Smith, Paul; Trotman, Judith; Viney, Zaid; Radford, John; Barrington, Sally. - In: NEW ENGLAND JOURNAL OF MEDICINE. - ISSN 0028-4793. - 374(2016), pp. 2419-2429. [10.1056/NEJMoa1510093]

Adapted treatment guided by interim PET-CT scan in advanced Hodgkin's lymphoma

FEDERICO, Massimo;FRANCESCHETTO, Antonella;LUMINARI, Stefano;
2016

Abstract

BACKGROUND: We tested interim positron-emission tomography-computed tomography (PET-CT) as a measure of early response to chemotherapy in order to guide treatment for patients with advanced Hodgkin's lymphoma. METHODS: Patients with newly diagnosed advanced classic Hodgkin's lymphoma underwent a baseline PETCT scan, received two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy, and then underwent an interim PET-CT scan. Images were centrally reviewed with the use of a 5-point scale for PET findings. Patients with negative PET findings after two cycles were randomly assigned to continue ABVD (ABVD group) or omit bleomycin (AVD group) in cycles 3 through 6. Those with positive PET findings after two cycles received BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone). Radiotherapy was not recommended for patients with negative findings on interim scans. The primary outcome was the difference in the 3-year progression-free survival rate between randomized groups, a noninferiority comparison to exclude a difference of 5 or more percentage points. RESULTS: A total of 1214 patients were registered; 937 of the 1119 patients (83.7%) who underwent an interim PET-CT scan according to protocol had negative findings. With a median follow-up of 41 months, the 3-year progression-free survival rate and overall survival rate in the ABVD group were 85.7% (95% confidence interval [CI], 82.1 to 88.6) and 97.2% (95% CI, 95.1 to 98.4), respectively; the corresponding rates in the AVD group were 84.4% (95% CI, 80.7 to 87.5) and 97.6% (95% CI, 95.6 to 98.7). The absolute difference in the 3-year progression-free survival rate (ABVD minus AVD) was 1.6 percentage points (95% CI, -3.2 to 5.3). Respiratory adverse events were more severe in the ABVD group than in the AVD group. BEACOPP was given to the 172 patients with positive findings on the interim scan, and 74.4% had negative findings on a third PET-CT scan; the 3-year progression-free survival rate was 67.5% and the overall survival rate 87.8%. A total of 62 patients died during the trial (24 from Hodgkin's lymphoma), for a 3-year progression-free survival rate of 82.6% and an overall survival rate of 95.8%. CONCLUSIONS: Although the results fall just short of the specified noninferiority margin, the omission of bleomycin from the ABVD regimen after negative findings on interim PET resulted in a lower incidence of pulmonary toxic effects than with continued ABVD but not significantly lower efficacy.
374
2419
2429
Adapted treatment guided by interim PET-CT scan in advanced Hodgkin's lymphoma / Johnson, Peter; Federico, Massimo; Kirkwood, Amy; Fosså, Alexander; Berkahn, Leanne; Carella, Angelo; D'Amore, Francesco; Enblad, Gunilla; Franceschetto, Antonella; Fulham, Michael; Luminari, Stefano; O'Doherty, Michael; Patrick, Pip; Roberts, Thomas; Sidra, Gamal; Stevens, Lindsey; Smith, Paul; Trotman, Judith; Viney, Zaid; Radford, John; Barrington, Sally. - In: NEW ENGLAND JOURNAL OF MEDICINE. - ISSN 0028-4793. - 374(2016), pp. 2419-2429. [10.1056/NEJMoa1510093]
Johnson, Peter; Federico, Massimo; Kirkwood, Amy; Fosså, Alexander; Berkahn, Leanne; Carella, Angelo; D'Amore, Francesco; Enblad, Gunilla; Franceschetto, Antonella; Fulham, Michael; Luminari, Stefano; O'Doherty, Michael; Patrick, Pip; Roberts, Thomas; Sidra, Gamal; Stevens, Lindsey; Smith, Paul; Trotman, Judith; Viney, Zaid; Radford, John; Barrington, Sally
File in questo prodotto:
File Dimensione Formato  
nejmoa1510093.pdf

non disponibili

Tipologia: Versione dell'editore (versione pubblicata)
Dimensione 626.67 kB
Formato Adobe PDF
626.67 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/1105342
Citazioni
  • ???jsp.display-item.citation.pmc??? 168
  • Scopus 463
  • ???jsp.display-item.citation.isi??? 436
social impact