Omitting Radiotherapy in Early Positron Emission Tomography–Negative Stage I/II Hodgkin Lymphoma Is Associated With an Increased Risk of Early Relapse: Clinical Results of the Preplanned Interim Analysis of the Randomized EORTC/LYSA/FIL H10 Trial

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.

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

Journal of Clinical Oncology ◽

10.1200/jco.2016.68.6394 ◽

2017 ◽

Vol 35 (16) ◽

pp. 1786-1794 ◽

Cited By ~ 191

Author(s):

Marc P.E. André ◽

Théodore Girinsky ◽

Massimo Federico ◽

Oumédaly Reman ◽

Catherine Fortpied ◽

...

Keyword(s):

Positron Emission Tomography ◽

Hodgkin Lymphoma ◽

Progression Free Survival ◽

Early Response ◽

Stage I ◽

Emission Tomography ◽

Combined Modality Treatment ◽

Excellent Outcome ◽

Combined Modality ◽

Positron Emission

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.

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Computed tomography and positron emission tomography/computed tomography surveillance after combined modality treatment of supradiaphragmatic Hodgkin lymphoma: a clinical and economic perspective

Leukemia & Lymphoma ◽

10.3109/10428194.2013.767902 ◽

2013 ◽

Vol 54 (10) ◽

pp. 2168-2176 ◽

Cited By ~ 11

Author(s):

Vatsal Patel ◽

Michael Buckstein ◽

Rodolfo Perini ◽

Christine Hill-Kayser ◽

Jakub Svoboda ◽

...

Keyword(s):

Computed Tomography ◽

Positron Emission Tomography ◽

Hodgkin Lymphoma ◽

Emission Tomography ◽

Combined Modality Treatment ◽

Economic Perspective ◽

Combined Modality ◽

Positron Emission

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Interim positron emission tomography in early stage Hodgkin lymphoma: is there evidence for its prognostic and predictive value in patients treated with standard combined modality treatment?

Leukemia & Lymphoma ◽

10.3109/10428194.2012.743658 ◽

2013 ◽

Vol 54 (6) ◽

pp. 1127-1128 ◽

Cited By ~ 1

Author(s):

Lena Specht

Keyword(s):

Positron Emission Tomography ◽

Hodgkin Lymphoma ◽

Predictive Value ◽

Early Stage ◽

Emission Tomography ◽

Combined Modality Treatment ◽

Combined Modality ◽

Positron Emission

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Prognostic Value of Positron Emission Tomography (PET) Scan in Patients with Relapsed Hodgkin Lymphoma or Aggressive Non-Hodgkin Lymphoma Receiving Salvage Chemotherapy Followed by Reduced-Intensity Allogeneic Stem Cell Transplantation.

Blood ◽

10.1182/blood.v110.11.3039.3039 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3039-3039 ◽

Cited By ~ 2

Author(s):

Anna Dodero ◽

Roberto Crocchiolo ◽

Francesca Patriarca ◽

Fabio Ciceri ◽

Nicolo’ Frungillo ◽

...

Keyword(s):

Positron Emission Tomography ◽

Hodgkin Lymphoma ◽

Prognostic Value ◽

Pet Scan ◽

Emission Tomography ◽

Non Hodgkin Lymphoma ◽

Positron Emission ◽

18F Fdg ◽

Pet Scans ◽

Reduced Intensity

Abstract Positron emission tomography (PET) scan using 18-fluorodeoxyglucose [18F-FDG] has a prognostic value in patients (pts) with Hodgkin Lymphoma (HL) or aggressive Non-Hodgkin lymphoma (NHL) receiving chemotherapy. Chemosensitive disease is a critical prognostic factor for the success of both autologous and allogeneic stem cell transplantation (allo-SCT). We have recently shown a lower risk of death or progression for pts in CR versus those in PR before reduced-intensity conditioning (RIC) allo-SCT (Corradini P, Leukemia 2007). Thus, to better assess the value of pre-transplant disease response, we retrospectively assessed the prognostic role of PET scan before allotransplant. Between 2000 and 2007, 64 consecutive patients with a histologically proven diagnosis of aggressive NHL [n=30: diffuse large B cell lymphoma (n=18), peripheral T-cell lymphomas (n=11), Burkitt lymphoma (n=1)] or HL [n=34], responding to salvage therapy, were evaluated with a PET scan before and after allo-SCT. PET scans were performed at 3 different Nuclear Medicine Units. Presence (PET-positive) or absence (PET-negative) of abnormal 18F-FDG uptake was correlated to progression-free survival (PFS) and overall survival (OS) curves. Patients’ median age was 37 years (range, 17–65 years). Thirty-three pts (52%) were allografted from a HLA-identical sibling donor, 14 from a haploidentical donor and 17 from an unrelated donor. Pts had relapsed disease: 52 pts (81%) had failed autologous SCT, the median number of prior chemotherapy regimens was 3 (range, 1–6). All pts received a RIC regimen followed by allo-SCT. PET scans were performed at a median of 30 days prior to allograft (range, 3–90 days): 34 out of 64 pts showed an abnormal 18F-FDG uptake [NHL (n=16), HL (n=18)] whereas 30 were completely negative [NHL (n=14), HL (n=16)]. Patients with PET-positive or PET-negative scans were balanced in terms of diagnosis, previous treatments, and type of donor. At a median follow-up of 24 months (range, 6–86 months), 41 pts are alive and 23 died [toxicity n=10 (n= 5 NHL, n=5 HL), disease n=13 (n=8 NHL, n=5 HL)]. Overall, the estimated 3-year PFS in pts with negative or positive PET scans were 64% (95% CI, 42%–86%) versus 28% (95% CI, 8%–48%), respectively (p<0.005). A statistically significant higher cumulative risk of relapse was observed in pts with a positive PET scan before allografting as compared to the PET negatives (53% versus 21%, p< 0.022). The estimated 3-year OS in pts with negative or positive PET scans were 69% (95% CI; 51%–87%) versus 44% (95% CI;23%-65%), respectively (p=0.05). For NHL pts, the estimated 3-year PFS was 59% for PET-negative as compared to 38% for PET-positive (p<0.04). For HL pts, the estimated 3-year PFS was 70% for PET-negative as compared to 23% for PET-positive (p<0.05). PET scan has a clinical relevance before allo-SCT. Pts with a positive PET scan have a worse outcome, and should receive experimental therapies to target chemoresistant tumor cells.

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Predicted Risks of Cardiovascular Disease Following Chemotherapy and Radiotherapy in the UK NCRI RAPID Trial of Positron Emission Tomography–Directed Therapy for Early-Stage Hodgkin Lymphoma

Journal of Clinical Oncology ◽

10.1200/jco.21.00408 ◽

2021 ◽

pp. JCO.21.00408

Author(s):

David J. Cutter ◽

Johanna Ramroth ◽

Patricia Diez ◽

Andy Buckle ◽

Georgios Ntentas ◽

...

Keyword(s):

Cardiovascular Disease ◽

Positron Emission Tomography ◽

Cardiovascular Risk ◽

Hodgkin Lymphoma ◽

Early Stage ◽

Emission Tomography ◽

Positron Emission ◽

Increased Risk ◽

Involved Field ◽

Involved Field Radiotherapy

PURPOSE The contemporary management of early-stage Hodgkin lymphoma (ES-HL) involves balancing the risk of late adverse effects of radiotherapy against the increased risk of relapse if radiotherapy is omitted. This study provides information on the risk of radiation-related cardiovascular disease to help personalize the delivery of radiotherapy in ES-HL. METHODS We predicted 30-year absolute cardiovascular risk from chemotherapy and involved field radiotherapy in patients who were positron emission tomography (PET)–negative following three cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy within a UK randomized trial of PET-directed therapy for ES-HL. Cardiac and carotid radiation doses and chemotherapy exposure were combined with established dose-response relationships and population-based mortality and incidence rates. RESULTS Average mean heart dose was 4.0 Gy (range 0.1-24.0 Gy) and average bilateral common carotid artery dose was 21.5 Gy (range 0.6-38.1 Gy), based on individualized cardiovascular dosimetry for 144 PET-negative patients receiving involved field radiotherapy. The average predicted 30-year radiation-related absolute excess overall cardiovascular mortality was 0.56% (range 0.01%-6.79%; < 0.5% in 67% of patients and > 1% in 15%), whereas average predicted 30-year excess incidence was 6.24% (range 0.31%-31.09%; < 5% in 58% of patients and > 10% in 24%). For cardiac disease, the average predicted 30-year radiation-related absolute excess mortality was 0.42% (0.79% with mediastinal involvement and 0.05% without) and for stroke, it was 0.14%. CONCLUSION Predicted excess cardiovascular risk is small for most patients, so radiotherapy may provide net benefit. However, for a minority of patients receiving high doses of radiation to cardiovascular structures, it may be preferable to consider advanced radiotherapy techniques to reduce doses or to omit radiotherapy and accept the increased relapse risk. Individual assessment of cardiovascular and other risks before treatment would allow personalized decision making about radiotherapy in ES-HL.

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Positive Positron Emission Tomography (PET) Scan in Non-Hodgkin Lymphoma Pre-Transplant Had No Impact On Relapse and Survival After Allogenenic Transplantation

Blood ◽

10.1182/blood.v120.21.1999.1999 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1999-1999

Author(s):

Veronika Bachanova ◽

Celalettin Ustun ◽

Qing Cao ◽

Froelich Jerry ◽

Linda J Burns

Keyword(s):

Positron Emission Tomography ◽

Follicular Lymphoma ◽

Hodgkin Lymphoma ◽

Relapse Rate ◽

Pet Imaging ◽

Pet Scan ◽

Emission Tomography ◽

Non Hodgkin Lymphoma ◽

Positron Emission

Abstract Abstract 1999 Allogeneic donor hematopoetic stem cell transplantation (HCT) is increasingly used for patients with non-Hodgkin lymphoma (NHL). Positron emission tomography (PET) has become a standard for lymphoma evaluation and a valuable prognostic tool to risk-stratify treatment and time of the autologous HCT. Role of PET imaging in allogeneic HCT setting is controversial. We sought to investigate the value of PET status pre-transplantation and at day 100 post donor HCT as an indicator predictive of relapse and survival post allograft. Seventy-three patients (median age 50 years [range 2–69 years]) with NHL received allogeneic HCT at University of Minnesota from 2004–2010 and had PET imaging within 4 weeks pre-transplant. All PET and CT images were reviewed centrally by nuclear medicine radiologist. Follicular lymphoma (n=26) was more common than large cell, mantle cell lymphoma and others. PET scan pre-transplant was positive in 44 patients (PET+ group 57% vs PET- group 43%). Two thirds of PET+ group were in partial remission (PR), 7% CR and 16% were chemo-refractory prior to transplant compared to 25% in PR, 68% in CR and 7% refractory in PET+ cohort (p<0.01). Forty percent had PET-avid extra-nodal involvement. In both PET positive and negative groups the two thirds received reduced intensity conditioning and related donor (52% and 51%) or umbilical cord blood grafts (55% and 41%, respectively). 5-years disease-free survival (DFS) and overall survival (OS) of the cohort was 51% (95%CI 35– 64%) and 60% (95%CI 44–73%). DFS and OS of PET+ group was similar to PET- group (DFS: 50% vs 52%, p=0.31; OS: 63% vs 56%, p=0.63). In univariate analysis, the lymphoma subtype, disease status at transplant, extranodal disease, elevated LDH, high B2 macroglobulin or marrow involvement at the time of transplant had no impact on survival or relapse rate. At median follow-up of 3.33 years (range 1.00–6.74) the cumulative 2 year relapse rate was 17%; similar in PET+ and PET- groups (19% [95% CI 7– 31%] vs 15% [95% CI 1– 28%]; p=0.48). Transplant mortality at 1-year was low for entire cohort (11% [95% CI 3–18%]) and particularly low in follicular lymphoma (4% [95%CI 0–10%]) compared to DL/MCL (10% [95%CI 0–21%]) and other NHL (25% [95%CI 4–46%]; p=0.51). PET status (pos vs neg) had no impact on grade III-IV acute GVHD and chronic GVHD. Fifty-four patients with available surveillance PET evaluation at day 100 post-transplant. The 1-year relapse rate and 5 yr DFS was significantly improved for those patient who were PET-negative (day 100 PET- vs PET+ group: relapse 9% vs 42%; p<0.01; DFS 57% vs 25%, p<0.01 and OS 68% vs 59%, p=0.63). In conclusion, pre-allo HCT PET scan for NHL does not predict transplant outcomes, however negative PET scan 100 days post-allo SCT is a valuable tool predictive of superior transplant DFS. Future studies evaluating role of PET in patients with specific lymphoma subsets and development of novel peri-transplant or post-transplant interventions for patients at high relapse risk are warranted. Disclosures: Off Label Use: decitabine for relapsed ALL vorinostat for relapsed ALL.

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Can Childhood Hodgkin International Prognostic Score Mitigate Interim Positron Emission Tomography and Predict Survival of Children with Hodgkin Lymphoma in Resource Limited Countries?

Blood ◽

10.1182/blood-2018-99-115822 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5370-5370

Author(s):

Reham Khedr ◽

Sally Mahfouz ◽

Hoda Fathy ◽

Lobna Shalaby

Keyword(s):

Positron Emission Tomography ◽

Hodgkin Lymphoma ◽

Prognostic Score ◽

Pet Scan ◽

Emission Tomography ◽

P Value ◽

Prognostic Role ◽

Positron Emission ◽

Therapeutic Decisions ◽

International Prognostic Score

Abstract Background & aim: Although 'interim' positron emission tomography (PET) may inform therapeutic decisions, Risk stratification at diagnosis allow earlier and potentially better modification during the treatment of HL. In this study, we aimed to identify the prognostic role of both the IPET and the CHIPS in predicting the prognosis of HL in our center. Patients and methods: This is a retrospective, single-center study done at the National Cancer Institute (NCI) Cairo University starting January 2011 to the end of December 2015. A total of 140 patients with newly diagnosed Hodgkin lymphoma were enrolled for analysis of all clinical, pathological and Laboratory Data. Only 83 patients were eligible for analysis of both IPET and CHIPS scoring. PET scan was performed at baseline and after two cycles of chemotherapy. Treatment was not changed according to the results of the interim scan. Childhood Hodgkin International Prognostic Score (CHIPS), was evaluated. Log-rank testing was used to compare EFS for each CHIPS (0-3). Results: Eight three scans out of 140 patients were eligible for analysis of both IPET and CHIPS scoring. Twenty-six patients were scored positive (31.3%) and 57 (68.7%) as negative. The 5- years overall survival (OS) was 94%, 83% for patients with interim positive scans and 97% for patients with interim negative scans (P 0.01). The 5-year Event-free survival (EFS) rate was 86.7% for the whole study population, 76% for patients with interim positive scans and 91% for patients with interim negative scans (P 0.04). The 5 year OS was 100% for patients with CHIPS = 0, 80.4% for patients with CHIPS = 1, 75% for patients with CHIPS = 2, and 100% for patients with CHIPS = 3 (a very limited number of patients), with a p-value of (0.055). Hemoglobin level </= 10) and initial Total Leucocytic count(</= 15,000) were independent prognostic predictors; OS P- value (0.003 and <0.001 ) respectively- and EFS P- value (0.03 and <0.001 ) respectively. Conclusion: The prognostic role and validity of using the interim PET scan response have been confirmed to be strongly related to treatment outcome by the present study; however, the use of CHIPS is a good inexpensive approach to predicting risk in patients with HL that may improve ability to tailor therapy to risk factors known at diagnosis. Other Variables including TLC as well as Hb level will need further larger studies to identify their impact. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

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Can Radiotherapy Be Omitted in Children With Hodgkin Lymphoma Who Achieve Metabolic Remission on Interim Positron Emission Tomography? Experience of a Tertiary Care Cancer Referral Center

Journal of Global Oncology ◽

10.1200/jgo.2017.009340 ◽

2018 ◽

pp. 1-7

Author(s):

Sidharth Totadri ◽

Venkatraman Radhakrishnan ◽

Trivadi S. Ganesan ◽

Prasanth Ganesan ◽

Krishnarathnam Kannan ◽

...

Keyword(s):

Positron Emission Tomography ◽

Hodgkin Lymphoma ◽

Tertiary Care ◽

Stage I ◽

Emission Tomography ◽

Bulky Disease ◽

Interim Pet ◽

Positron Emission ◽

Response To Chemotherapy ◽

Pet Ct

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.

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