Article

Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): A randomised, open-label, phase 3 non-inferiority trial

University Hospital of Cologne, Department of Internal Medicine I, Köln, Germany.
The Lancet (Impact Factor: 45.22). 04/2012; 379(9828):1791-9. DOI: 10.1016/S0140-6736(11)61940-5
Source: PubMed

ABSTRACT

The intensity of chemotherapy and need for additional radiotherapy in patients with advanced stage Hodgkin's lymphoma has been unclear. We did a prospective randomised clinical trial comparing two reduced-intensity chemotherapy variants with our previous standard regimen. Chemotherapy was followed by PET-guided radiotherapy.
In this parallel group, open-label, multicentre, non-inferiority trial (HD15), 2182 patients with newly diagnosed advanced stage Hodgkin's lymphoma aged 18-60 years were randomly assigned to receive either eight cycles of BEACOPP(escalated) (8×B(esc) group), six cycles of BEACOPP(escalated) (6×B(esc) group), or eight cycles of BEACOPP(14) (8×B(14) group). Randomisation (1:1:1) was done centrally by stratified minimisation. Non-inferiority of the primary endpoint, freedom from treatment failure, was assessed using repeated CIs for the hazard ratio (HR) according to the intention-to-treat principle. Patients with a persistent mass after chemotherapy measuring 2·5 cm or larger and positive on PET scan received additional radiotherapy with 30 Gy; the negative predictive value for tumour recurrence of PET at 12 months was an independent endpoint. This trial is registered with Current Controlled Trials, number ISRCTN32443041.
Of the 2182 patients enrolled in the study, 2126 patients were included in the intention-to-treat analysis set, 705 in the 8×B(esc) group, 711 in the 6×B(esc) group, and 710 in the 8×B(14) group. Freedom from treatment failure was sequentially non-inferior for the 6×B(esc) and 8×B(14) groups as compared with 8×B(esc). 5-year freedom from treatment failure rates were 84·4% (97·5% CI 81·0-87·7) for the 8×B(esc) group, 89·3% (86·5-92·1) for 6×B(esc) group, and 85·4% (82·1-88·7) for the 8×B(14) group (97·5% CI for difference between 6×B(esc) and 8×B(esc) was 0·5-9·3). Overall survival in the three groups was 91·9%, 95·3%, and 94·5% respectively, and was significantly better with 6×B(esc) than with 8×B(esc) (97·5% CI 0·2-6·5). The 8×B(esc) group showed a higher mortality (7·5%) than the 6×B(esc) (4·6%) and 8×B(14) (5·2%) groups, mainly due to differences in treatment-related events (2·1%, 0·8%, and 0·8%, respectively) and secondary malignancies (1·8%, 0·7%, and 1·1%, respectively). The negative predictive value for PET at 12 months was 94·1% (95% CI 92·1-96·1); and 225 (11%) of 2126 patients received additional radiotherapy.
Treatment with six cycles of BEACOPP(escalated) followed by PET-guided radiotherapy was more effective in terms of freedom from treatment failure and less toxic than eight cycles of the same chemotherapy regimen. Thus, six cycles of BEACOPP(escalated) should be the treatment of choice for advanced stage Hodgkin's lymphoma. PET done after chemotherapy can guide the need for additional radiotherapy in this setting.
Deutsche Krebshilfe and the Swiss Federal Government.

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    • "In addition , for all patients enrolled into HD13, HD14 and NLPHL- IA, initial CT scans were sent to the University Hospital of Cologne, where a panel of experts in imaging and radiation oncology re-evaluated the initial findings and developed an IFRT plan for each individual patient. In the HD15 trial, initial imaging was only reviewed in patients with a residual mass ≥2Á5 cm after completion of chemotherapy (% 1 / 3 of patients), because the protocol treatment did not routinely include IFRT (Engert et al, 2012). Incorrect allocation to a trial either revealed by the GHSG trial physician or the imaging panel, or based on a correction of initial findings reported to the TCC by the local physician, was documented in the trial database. "
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    ABSTRACT: Patients, methods: The analysis set consisted of 739 patients with residues ≥ 2.5 cm after 6 or 8 cycles of BEACOPPesc from the HD15 trial performed by the German Hodgkin Study Group. The recommendation for or against further radiotherapy was based on the central [18F]FDG-PET interpretation. Central PET interpretation was compared to the local PET interpretation and concordance was measured using Cohen's Kappa coefficient. Prognostic impact of the analysis of concordance between local and central PET interpretations was evaluated using progression free survival (PFS); groups were compared with the log rank test. Results: The central panel rated 548 of 739 patients (74%) as PET negative. Of these, 513 were also rated as PET negative in the local PET interpretation. PET positivity was seen by central reviewers in the remaining 191 patients (26%), in concordance with local reviewers in 155 cases. Even though substantial agreement was found (Cohen's Kappa 0.81), the interpretation of the central PET review panel led to a different therapeutic recommendation in 71/739 (10%) patients. PFS was equally high in groups in which the therapeutic regime had been changed on the basis of the central panel decision. Conclusion: High concordance is found between local and central reviewers with regard to PET interpretation in residual tissue after intense chemotherapy. The existence of the central PET review panel allows the identification of additional patients as PET negative so that radiotherapy can be safely omitted (35 of 548 patients = 4.7%).
    No preview · Article · Sep 2015 · Nuklearmedizin
    • "In addition , for all patients enrolled into HD13, HD14 and NLPHL- IA, initial CT scans were sent to the University Hospital of Cologne, where a panel of experts in imaging and radiation oncology re-evaluated the initial findings and developed an IFRT plan for each individual patient. In the HD15 trial, initial imaging was only reviewed in patients with a residual mass ≥2Á5 cm after completion of chemotherapy (% 1 / 3 of patients), because the protocol treatment did not routinely include IFRT (Engert et al, 2012). Incorrect allocation to a trial either revealed by the GHSG trial physician or the imaging panel, or based on a correction of initial findings reported to the TCC by the local physician, was documented in the trial database. "
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    ABSTRACT: Accurate clinical staging is crucial for adequate risk-adapted treatment in Hodgkin lymphoma (HL) to prevent patients from under- or over-treatment. Within the latest German Hodgkin Study Group trial generation, diagnostic findings such as histopathology, computerized tomography imaging and clinical risk factors were re-evaluated by expert panels. Here, we retrospectively analysed 5965 patients and identified 399 in who major discordant findings changed their first-line treatment allocation. Histopathology review did not confirm the initial diagnosis of HL in 87 patients. Treatment allocation was revised in 312 of the remaining 5878 patients: 176 were assigned to a higher and 128 to a lower risk group, respectively; the correct treatment group remained unclear in 8 patients. Cases of revised treatment allocation accounted for 9·8%, 6·0%, 0·8%, and 14·8% of patients initially assigned to the HD13, HD14, HD15 trials and stage IA lymphocyte-predominant HL project, respectively. Most revisions were due to wrong application of clinical stage (20·5% of 312 patients with revised treatment group), histological subtype (9·0%) or the risk factors ≥3 involved areas (46·8%) or large mediastinal mass (9·3%). In conclusion, centralized review by experienced experts changed risk-adapted first-line treatment in a relevant proportion of HL patients. Quality control measures clearly improve the accuracy of treatment and should be implemented in clinical practice. © 2015 John Wiley & Sons Ltd.
    No preview · Article · Aug 2015 · British Journal of Haematology
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    • "Ultrasound, CT and magnetic resonance imaging have become the preferred methods for identifying adrenal tumors. PET-CT is not only able to distinguish between benign and malignant tumors of the adrenal gland in order to make a diagnosis, but also plays a significant role in the staging, evaluation of therapeutic effects and prediction of patient prognosis in HL (13). "
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    ABSTRACT: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a subtype of Hodgkin lymphoma (HL), and is a rare disease manifestation in the adrenal gland, which is difficult to be diagnosed and treated. In the present study, we report a case of primary adrenal NLPHL in a 36-year-old male patient. The patient was without specific clinical signs and the definitive diagnosis was achieved by histological study. The patient underwent a laparoscopic left adrenalectomy and chemotherapy regimen of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). There is no standard treatment for adrenal NLPHL and therefore, treatment is based on that for other types of NLPHL, which includes radiotherapy and ABVD chemotherapy. Given the rarity of this disease, there are limited experiences with regard to its diagnosis and treatment. This study is useful for the differential diagnosis and treatment of adrenal masses.
    Full-text · Article · Sep 2014 · Oncology letters
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