title: Phase II study of interim PET-CT-guided response-adapted therapy in advanced Hodgkin's lymphoma.
abstract: BACKGROUND
  Combination chemotherapy ABVD (doxorubicin, bleomycin, vinblastine and dacarabazine) cures ∼70% of patients with advanced Hodgkin's lymphoma (aHL, stages IIB, III and IV) while more toxic escalated BEACOPP (EB, combination of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisolone) increases cure rates to 85%. Patients with a positive interim positron emission tomography-computerized tomography (PET-CT) scan after two cycles (PET-2) of ABVD have very poor outcomes with continued ABVD. Intensifying therapy with EB in PET-2-positive patients ('response-adapted therapy') may improve cure rates, whereas the negative patients can continue ABVD alone.
  
  
  METHODS
  Eligible patients with newly diagnosed aHL received two cycles of ABVD and underwent PET-2 (scored with semi-quantitative 5-point visual criteria, 'Deauville score'). PET-2-negative patients continued four additional cycles of ABVD, whereas PET-2-positive patients received four cycles of EB. A phase II sample size of 50 was estimated keeping the lower and higher proportion of rejection of the event-free survival (EFS) as 70% and 85%, respectively.
  
  
  RESULTS
  Fifty patients [median age 28 (12-60) years; male : female: 39 : 11; stages: IIB-3 (6%), III-29 (58%) and IV-18 (36%); International Prognostic Score (IPS): 0-3: 34 (68%); 4-7: 16 (32%)] were enrolled; 49 underwent PET-2. Eight (16%) were PET-2-positive, whereas 41 (84%) were negative. Forty-seven were evaluable for EFS and all 50 for overall survival (OS). The 2-year EFS was 76% (95% CI: 68-83) and OS was 88% (95% CI: 82-94). PET-2 was strongly prognostic-2-year EFS, negative versus positive: 82% versus 50%; P = 0.013.
  
  
  CONCLUSIONS
  PET-2 response-adapted strategy could not achieve EFS of 85% in aHL. However, escalated therapy improved outcomes in PET-2-positive patients compared with historical data.
  
  
  BACKGROUND
  CTRI/2012/06/002741 (http://www.ctri.nic.in) and NCT01304849 (http://www.clinicaltrials.gov).
authors.affiliation: Department of Medical Oncology. Electronic address: prasanth.ganesan@cancerinstitutewia.org.
authors.forename: P
authors.initials: P
authors.lastname: Ganesan
authors.affiliation: Department of Medical Oncology.
authors.forename: R
authors.initials: R
authors.lastname: Rajendranath
authors.affiliation: Department of Medical Oncology.
authors.forename: K
authors.initials: K
authors.lastname: Kannan
authors.affiliation: Department of Medical Oncology.
authors.forename: V
authors.initials: V
authors.lastname: Radhakrishnan
authors.affiliation: Department of Medical Oncology.
authors.forename: T S
authors.initials: TS
authors.lastname: Ganesan
authors.affiliation: Department of Medical Oncology.
authors.forename: K
authors.initials: K
authors.lastname: Udupa
authors.affiliation: Department of PET-CT Scan Center.
authors.forename: K M
authors.initials: KM
authors.lastname: Lakshmipathy
authors.affiliation: Department of Radiodiagnosis.
authors.forename: V
authors.initials: V
authors.lastname: Mahajan
authors.affiliation: Department of Pathology.
authors.forename: S
authors.initials: S
authors.lastname: Sundersingh
authors.affiliation: Department of Tumor Registry, Cancer Institute (WIA), Chennai, India.
authors.forename: S
authors.initials: S
authors.lastname: Rajaraman
authors.affiliation: Department of Nuclear Medicine.
authors.forename: R
authors.initials: R
authors.lastname: Krishnakumar
authors.affiliation: Department of Medical Oncology.
authors.forename: T G
authors.initials: TG
authors.lastname: Sagar
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006689:Hodgkin Disease / Q000000981:diagnostic imaging / Q000188:drug therapy*; D006801:Humans; D007194:India; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011344:Procarbazine / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
chemical_list: D001761:Bleomycin; D011344:Procarbazine; D014750:Vincristine; D014747:Vinblastine; D005047:Etoposide; D003606:Dacarbazine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
keywords: ABVD; Deauville score; Hodgkin's lymphoma; escalated BEACOPP; interim PET–CT scan; response-adapted therapy