Faculty Opinions recommendation of Early Positron Emission Tomography Response-Adapted Treatment in Stage I and II Hodgkin Lymphoma: Final Results of the Randomized EORTC/LYSA/FIL H10 Trial.

Author(s):  
Boris Böll
2017 ◽  
Vol 35 (16) ◽  
pp. 1786-1794 ◽  
Author(s):  
Marc P.E. André ◽  
Théodore Girinsky ◽  
Massimo Federico ◽  
Oumédaly Reman ◽  
Catherine Fortpied ◽  
...  

Purpose Patients who receive combined modality treatment for stage I and II Hodgkin lymphoma (HL) have an excellent outcome. Early response evaluation with positron emission tomography (PET) scan may improve selection of patients who need reduced or more intensive treatments. Methods We performed a randomized trial to evaluate treatment adaptation on the basis of early PET (ePET) after two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in previously untreated—according to European Organisation for Research and Treatment of Cancer criteria favorable (F) and unfavorable (U)—stage I and II HL. The standard arm consisted of ABVD followed by involved-node radiotherapy (INRT), regardless of ePET result. In the experimental arm, ePET-negative patients received ABVD only (noninferiority design), whereas ePET-positive patients switched to two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPesc) and INRT (superiority design). Primary end point was progression-free survival (PFS). Results Of 1,950 randomly assigned patients, 1,925 received an ePET—361 patients (18.8%) were positive. In ePET-positive patients, 5-year PFS improved from 77.4% for standard ABVD + INRT to 90.6% for intensification to BEACOPPesc + INRT (hazard ratio [HR], 0.42; 95% CI, 0.23 to 0.74; P = .002). In ePET-negative patients, 5-year PFS rates in the F group were 99.0% versus 87.1% (HR, 15.8; 95% CI, 3.8 to 66.1) in favor of ABVD + INRT; the U group, 92.1% versus 89.6% (HR, 1.45; 95% CI, 0.8 to 2.5) in favor of ABVD + INRT. For both F and U groups, noninferiority of ABVD only compared with combined modality treatment could not be demonstrated. Conclusion In stage I and II HL, PET response after two cycles of ABVD allows for early treatment adaptation. When ePET is positive after two cycles of ABVD, switching to BEACOPPesc + INRT significantly improved 5-year PFS. In ePET-negative patients, noninferiority of ABVD only could not be demonstrated: risk of relapse is increased when INRT is omitted, especially in patients in the F group.


2018 ◽  
pp. 1-7
Author(s):  
Sidharth Totadri ◽  
Venkatraman Radhakrishnan ◽  
Trivadi S. Ganesan ◽  
Prasanth Ganesan ◽  
Krishnarathnam Kannan ◽  
...  

Purpose Treating pediatric Hodgkin lymphoma (HL) involves a delicate balance between cure and reducing late toxicity. Fluorodeoxyglucose positron emission tomography (PET) combined with computed tomography (CT) identifies patients with early response to chemotherapy, for whom radiotherapy may be avoided. The role of PET-CT in upfront risk stratification and response–adapted treatment is evaluated in this study. Methods Patients with HL, who were younger than 18 years, were included. PET-CT was performed at baseline and after two cycles of chemotherapy. Patients were stratified into three risk groups: group 1 (stage I or II with no unfavorable features); group 2 (stage I or II with bulky disease/B symptoms); and group 3 (stage III/IV). A doxorubicin, bleomycin, vinblastine, dacarbazine–based regimen was used in early disease. A cyclophosphamide, vincristine, prednisolone, procarbazine, doxorubicin, bleomycin, vinblastine–based regimen was used in advanced disease. Results Forty-nine patients were included. Fifteen (31%), seven (14%), and 27 (55%) patients were included in groups 1, 2, and 3, respectively. Among 36 patients who underwent staging by PET-CT at diagnosis, seven (19%) patients were upstaged and one (3%) patient was downstaged by PET compared with CT. On the basis of negative interim PET responses, 39 (80%) patients were treated without radiotherapy. The 3-year event-free survival for the entire cohort was 91% (± 5.2%) and overall survival was 100%. Conclusion PET-CT is an excellent stand-alone staging modality in HL. The omission of radiotherapy can be considered in patients who achieve metabolic remission on interim PET.


2014 ◽  
Vol 32 (12) ◽  
pp. 1188-1194 ◽  
Author(s):  
John M.M. Raemaekers ◽  
Marc P.E. André ◽  
Massimo Federico ◽  
Theodore Girinsky ◽  
Reman Oumedaly ◽  
...  

Purpose Combined-modality treatment is standard treatment for patients with clinical stage I/II Hodgkin lymphoma (HL). We hypothesized that an early positron emission tomography (PET) scan could be used to adapt treatment. Therefore, we started the randomized EORTC/LYSA/FIL Intergroup H10 trial evaluating whether involved-node radiotherapy (IN-RT) could be omitted without compromising progression-free survival in patients attaining a negative early PET scan after two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) as compared with standard combined-modality treatment. Patients and Methods Patients age 15 to 70 years with untreated clinical stage I/II HL were eligible. Here we report the clinical outcome of the preplanned interim futility analysis scheduled to occur after documentation of 34 events in the early PET–negative group. Because testing for futility in this noninferiority trial corresponds to testing the hypothesis of no difference, a one-sided superiority test was conducted. Results The analysis included 1,137 patients. In the favorable subgroup, 85.8% had a negative early PET scan (standard arm, one event v experimental arm, nine events). In the unfavorable subgroup, 74.8% had a negative early PET scan (standard arm, seven events v experimental arm, 16 events). The independent data monitoring committee concluded it was unlikely that we would show noninferiority in the final results for the experimental arm and advised stopping random assignment for early PET–negative patients. Conclusion On the basis of this analysis, combined-modality treatment resulted in fewer early progressions in clinical stage I/II HL, although early outcome was excellent in both arms. The final analysis will reveal whether this finding is maintained over time.


Author(s):  
René-Olivier Casasnovas ◽  
Reda Bouabdallah ◽  
Pauline Brice ◽  
Julien Lazarovici ◽  
Hervé Ghesquieres ◽  
...  

PURPOSE The AHL2011 study (ClinicalTrials.gov identifier: NCT01358747 ) demonstrated that a positron emission tomography (PET)-driven de-escalation strategy after two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) provides similar progression-free survival (PFS) and overall survival (OS) and reduces early toxicity compared with a nonmonitored standard treatment. Here, we report, with a prolonged follow-up, the final study results. METHODS Patients with advanced Hodgkin lymphoma (stage III, IV, or IIB with mediastinum/thorax ratio > 0.33 or extranodal involvement) age 16-60 years were prospectively randomly assigned between 6 × BEACOPP and a PET-driven arm after 2 × BEACOPP delivering 4 × ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) in PET2– and 4 × BEACOPP in PET2+ patients. PET performed after four cycles of chemotherapy had to be negative to complete the planned treatment. RESULTS In total, 823 patients were enrolled including 413 in the standard arm and 410 in the PET-driven arm. With a 67.2-month median follow-up, 5-year PFS (87.5% v 86.7%; hazard ratio [HR] = 1.07; 95% CI, 0.74 to 1.57; P = .67) and OS (97.7% in both arms; HR = 1.012; 95% CI, 0.50 to 2.10; P = .53) were similar in both randomization arms. In the whole cohort, full interim PET assessment predicted patients' 5-year PFS (92.3% in PET2–/PET4–, 75.4% [HR = 3.26; 95% CI, 18.3 to 5.77] in PET2+/PET4– and 46.5% [HR = 12.4; 95% CI, 7.31 to 19.51] in PET4+ patients, respectively; P < .0001) independent of international prognosis score. Five-year OS was also affected by interim PET results, and PET2+/PET4– patients (93.5%; HR = 3.3; 95% CI, 1.07 to 10.1; P = .036) and PET4+ patients (91.9%; HR = 3.756; 95% CI, 1.07 to 13.18; P = .038) had a significant lower OS than PET2–/PET4– patients (98.2%). Twenty-two patients (2.7%) developed a second primary malignancy, 13 (3.2%) and 9 (2.2%) in the standard and experimental arms, respectively. CONCLUSION The extended follow-up confirms the continued efficacy and favorable safety of AHL2011 PET-driven strategy, which is noninferior to standard six cycles of BEACOPP. PET4 provides additional prognostic information to PET2 and allows identifying patients with particularly poor prognosis.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6018-6018
Author(s):  
Noam Avraham VanderWalde ◽  
Ramzi George Salloum ◽  
Tsai-Ling Liu ◽  
Mark Christopher Hornbrook ◽  
Maureen Cecelia O'Keeffe-Rosetti ◽  
...  

6018 Background: Positron emission tomography (PET) is often used for the staging of head and neck cancer (HNC). The purpose of this study is to explore the association between the increased utilization of PET and stage/survival in the managed care environment. Methods: Adult patients diagnosed with HNC (n=958) between 2000-2008, at 4 integrated health systems (Group Health Cooperative, Seattle; Health Alliance Plan/Henry Ford Health System, Detroit; Kaiser Permanente Colorado and Northwest, Portland) were identified via tumor registries linked to claims data. We compared AJCC stage distribution, patient/treatment characteristics, and survival between pre-PET era (2000-2004) vs. PET era (2005-2008), and those with PET vs. those without, during the PET era. AJCC stage was grouped into stage I/II (localized), stage III/IVa/IVb (locally advanced), and stage IVc (metastatic). Ordered logistic regression estimated the effects of PET utilization on upstaging. Kaplan-Meier estimates described overall survival (OS) differences between PET users and nonusers in the PET era. Cox proportional hazards regression evaluated the effect of PET use on survival. Results: There was a non-significant increase in stage III/IVa/IVb (40% to 44%) with a decrease in stage I/II (58% to 52%) between pre-PET era and PET era (p=0.11). During the PET era, patients with PET were more likely stage III/IVa/IVb and less likely stage I/II compared to patients without PET (III/IVa/IVb: 62% vs. 29%, I/II: 35% vs. 68%). On multivariate analysis those who were staged with PET were twice as likely to have locally advanced disease (OR 2.091; p=0.006). There was no difference in stage IVc. Patients with PET scans were more likely to receive chemotherapy with radiation and less likely to receive no treatment. 3-year actuarial OS for patients (all stages) with and without PET was 81% vs. 77% (p=0.261). 3-year actuarial OS for patients staged III/IVa/IVb with and without PET was 58% vs. 41% (p= 0.001). Conclusions: HNC patients were more likely to be upstaged with the use of PET. There was an improvement in survival in stage III/IVa/IVb patients, but no difference in survival across all stages. This likely reflects selection bias and stage migration rather than improved outcomes among individual patients.


2013 ◽  
Vol 04 (03) ◽  
pp. 452-459 ◽  
Author(s):  
Luis F. Porrata ◽  
Kay M. Ristow ◽  
Thomas M. Habermann ◽  
Thomas E. Witzig ◽  
Joseph P. Colgan ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document