scholarly journals Modification of initial therapy in early and advanced Hodgkin lymphoma, based on interim PET/CT is beneficial: a prospective multicentre trial of 355 patients

2017 ◽  
Vol 178 (5) ◽  
pp. 709-718 ◽  
Author(s):  
Eldad J. Dann ◽  
Osnat Bairey ◽  
Rachel Bar-Shalom ◽  
Tanya Mashiach ◽  
Elinor Barzilai ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Multicentre Trial ◽  
Initial Therapy ◽  
Interim Pet ◽  
Pet Ct

scholarly journals ADVANCED HODGKIN LYMPHOMA: A NEW ERA OF THERAPY

2014 ◽  
Vol 6 (1) ◽  
pp. e2014063 ◽  
Author(s):  
Eldad J Dann
Keyword(s):  
Hodgkin Lymphoma ◽  
Prognostic Score ◽  
Progression Free Survival ◽  
Initial Therapy ◽  
Free Survival ◽  
New Era ◽  
Interim Pet ◽  
Pet Ct ◽  
Multiple Issues ◽  
International Prognostic Score

Therapy of advanced Hodgkin lymphoma (HL) is a rapidly changing field due to a lot of currently emerging data. Treatment approaches are presently based on either the Kairos principle of giving aggressive therapy upfront and considering de-escalation of therapy if the interim PET/CT is negative or the Chronos principle of starting with ABVD followed by escalation of therapy for patients with positive interim PET/CT. The International Prognostic Score (IPS) is still valid for decision-making regarding the type of initial therapy, since patients with a high score do have an inferior progression free survival (PFS) with ABVD compared to those with a low score. Escalated BEACOPP administered upfront improves PFS; however, increase in the overall survival (OS) has not been confirmed yet, and this therapy is accompanied by elevated toxicity and fertility impairment. Completion of ongoing and currently initiated trials could elucidate multiple issues related to the management of HL patients.  

Risk-Adapted Treatment of Advanced Hodgkin Lymphoma With PET-CT

2016 ◽  
pp. e376-e385
Author(s):  
Ryan C. Lynch ◽  
Ranjana H. Advani
Keyword(s):  
Hodgkin Lymphoma ◽  
Adaptive Design ◽  
Response Assessment ◽  
Early Response ◽  
Clinical Criteria ◽  
Interim Pet ◽  
Early Results ◽  
Pet Ct ◽  
Risk Patients ◽  
Early Response Assessment

Although patients with advanced-stage classic Hodgkin lymphoma have excellent outcomes with contemporary therapy, the outcomes of patients with refractory disease is suboptimal. Identification of these high-risk patients at diagnosis is challenging as the differences in outcomes using clinical criteria are less marked using current modern therapy. Data suggest that an interim PET-CT may be a powerful tool in risk-stratifying patients. Retrospective studies show that a negative interim PET-CT after two to four cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) is predictive of favorable outcome independent of IPS score. Currently, there are several ongoing trials that aim to determine whether early-response assessment can be used to select patients who might benefit from modifications of subsequent therapy, either by intensifying or abbreviating regimens and/or omitting radiotherapy with promising early results. Longer follow-up is required to assess whether this strategy impacts overall survival (OS). Herein, we review the results of recent trials using interim PET-CT-based adaptive design in the treatment of advanced HL.

Interim FDG PET Imaging in CALGB 50203 Trial of Stage I/II Non-Bulky Hodgkin Lymphoma: Would Using Combined PET and CT Criteria Better Predict Response Than Each Test Alone?,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3644-3644 ◽  
Author(s):  
Lale Kostakoglu ◽  
Heiko Schoder ◽  
Nathan Hall ◽  
David J. Straus ◽  
Jeffrey L Johnson ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Hodgkin Lymphoma ◽  
Fdg Pet ◽  
Research Funding ◽  
Roc Analysis ◽  
Stage I ◽  
Advisory Committees ◽  
Interim Pet ◽  
Number Of Patients ◽  
Pet Ct

Abstract Abstract 3644 Use of interim PET in Hodgkin Lymphoma (HL) for risk-adapted treatment has been confounded by a lack of standardized criteria for interpretation. The International Harmonisation Project (IHP) criteria (JCO 2007;25:571) have been validated and are widely used for restaging following therapy. Our objective was to validate the IHP criteria for response evaluation based on PET after two cycles and correlate with the “London”criteria and diagnostic CT-based (dCT) lesion size changes. Methods: Pts were accrued prospectively to CALGB 50203, a trial of doxorubicin, vinblastine and gemcitabine (AVG) for initial treatment of stage I-II non-bulky Hodgkin lymphoma (HL). All had FDG PET or PET/CT and a separate high-resolution dCT scan at baseline, after two cycles of AVG (PET-2 and dCT-2) and at the end of therapy. No treatment change was made based on the PET-2 results. Of 99 assessable pts, 88 had both PET-2 and dCT-2. The primary PET-2 interpretation was based on IHP criteria (uptake > mediastinal blood pool/background is positive), a secondary interpretation was performed using the 5 point London criteria (uptake > liver is positive). The percent decrease in the sum of the products of the diameter (%SPPD) was determined between baseline dCT and dCT-2. A receiver operator curve (ROC) analysis was performed to determine the best cut-off for %SPPD to define a positive and negative CT result. The PET-2 and dCT-2 (%SPPD change) data were correlated with progression free survival (PFS). Results: Sixty-four pts (73%) achieved a complete remission (CR)/CR unconfirmed (CRu), 23.9% a partial response (PR), and 3% had stable disease. After a median follow-up of 3.3 years (1.8–5.0 years), 23.9% of patients relapsed/progressed with an estimated 3-year PFS of 0.77 [CI 68,84]. Eleven of 24 (45.8%) PET-2 positive patients relapsed vs. 10 of 64 (15.6%) PET-2 negative patients (p=0.0004). The best cut-off determined from ROC analysis for %SPPD change was 65%. The comparative results for individual evaluation criteria are displayed in the Table. In the PET-2 positive group, a negative dCT-2 increased PFS by 27–35%, suggesting an influence from dCT-2 results. However, in the combinatorial analysis, some of the confidence intervals are large due to small number of patients in each individual group, particularly, when both PET-2 and dCT-2 were positive as well as when PET-2 was positive and dCT-2 was negative. Conclusions: Interim PET/CT after two cycles of chemotherapy using either IHP or London criteria has a high NPV in early stage non-bulky HL. However, the PPV of interim PET needs to be improved to guide clinical management. Combining PET-2 with %SPPD decrease after 2 cycles improves prediction of PFS compared to each test alone. These data provide a proof of concept for risk-adapted clinical trials and further studies are underway to confirm these findings in a larger population. Disclosures: Bartlett: seattle genetics: Research Funding. Cheson:Celphalon: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celegen: Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Research Funding.

scholarly journals How does PET/CT help in selecting therapy for patients with Hodgkin lymphoma?

Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 322-327 ◽  
Author(s):  
Martin Hutchings
Keyword(s):  
Hodgkin Lymphoma ◽  
Early Response ◽  
Precise Determination ◽  
Disease Extent ◽  
Interim Pet ◽  
First Line Therapy ◽  
Positron Emission ◽  
Pet Ct ◽  
Consolidation Radiotherapy ◽  
Selection Of

Abstract Positron emission tomography/computed tomography (PET/CT) has emerged as the most accurate tool for staging, treatment monitoring, and response evaluation in Hodgkin lymphoma (HL). Accurate staging and restaging are very important for the optimal management of HL, but we are only beginning to understand how to use PET/CT to improve treatment outcome. More precise determination of disease extent may result in more precise pretreatment risk stratification, and is also essential for the minimal and highly individualized radiotherapy volumes of the present era. Several trials are currently investigating the use of PET/CT for early response-adapted therapy, with therapeutic stratification based on interim PET/CT results. Posttreatment PET/CT is a cornerstone of the revised response criteria and enables the selection of advanced-stage patients without the need for consolidation radiotherapy. Once remission is achieved after first-line therapy, PET/CT seems to have little or no role in the routine surveillance of HL patients. PET/CT looks promising for the selection of therapy in relapsed and refractory disease, but its role in this setting is still unclear.

scholarly journals Can We Improve the Predictive Value of Interim PET/CT Using a New Prognostic Model for Advanced Hodgkin Lymphoma?

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3001-3001
Author(s):  
Eldad J. Dann ◽  
Osnat Bairey ◽  
Rachel Bar-Shalom ◽  
Tanya Mashiach ◽  
Elinor Barzilai ◽  
...  
Keyword(s):  
Risk Factors ◽  
Radiation Therapy ◽  
Disease Progression ◽  
Hodgkin Lymphoma ◽  
Lymphocyte Count ◽  
Prognostic Score ◽  
Univariate Analysis ◽  
Disease Stage ◽  
Interim Pet ◽  
Pet Ct

Abstract Introduction: The treatment of advanced Hodgkin lymphoma (HL) has undergone many changes in recent years. The original International Prognostic Score (IPS) introduced by Hasenclever et al (1998) was based on a cohort of 1618 patients (pts) mainly treated with MOPP-ABV or ABVD between the years 1983 and 1992. One third (33%) of those pts also underwent involved field radiation therapy (IFRT). Staging was based on CT. The 5-y freedom from progression (FFP) results ranged between 84% and 42%, depending on the presence of 0-≥5 risk factors. The IPS has been validated in a number of studies and settings. Currently, staging is based on baseline PET/CT, which upgrades the disease stage in 15% and downgrades it in 5% of pts compared to CT scan. Positive interim PET/CT (PET-2) is predictive of an inferior prognosis in pts with early and advanced HL. Based on these findings, several studies have used a positive PET-2 as an indication for therapy escalation. However, the majority of relapses still occur in pts with negative PET-2, highlighting the need for additional prognostic markers. We evaluated baseline factors and lab results in a prospectively collected database of pts enrolled in a multicenter clinical trial (NCT00392314) where treatment was modified based on PET-2 results. The current study aimed to develop a model for refined prediction of HL progression risk in advance-disease pts with negative PET-2, using baseline risk factors. Methods: Pts with advanced classic Hodgkin lymphoma (HL) were stratified according to their baseline IPS; treatment was modified according to PET-2 results. Pts with IPS 0-2 initially received 2 ABVD cycles and those with IPS ≥ 3 received 2 cycles of escalated BEACOPP (EB). In the former group, if PET-2 was positive without evidence of disease progression, therapy was escalated to EB with involved site radiation therapy (ISRT) given to residual masses. If PET-2 was negative in both IPS strata, 4 additional ABVD cycles were administered. We evaluated whether traditional IPS parameters continued to predict relapse when treatment was modified based on PET-2 results, and assessed the need for new cutoffs based on ROC curves using univariate and multivariate Cox proportional hazard models. Results: Of 185 enrolled pts, 33 (18%) experienced disease progression and 27 (15%) had a positive PET-2. The 5-y PFS for the whole group, PET-2 negative and PET-2 positive subgroups was 80%, 82% and 68%, respectively (p=0.07). Eight of 33 (28%) relapsed pts had a positive Deauville score (≥3). On univariate analysis of traditional IPS parameters, male gender, age >45, stage IV disease were not found to be associated with a significantly increased hazard ratio (HR) for progression. New cutoffs for lymphocyte count and albumin level predictive of relapse were determined. The following parameters were significantly (P<0.006) associated with lower PFS on univariate analysis: albumin <3.5gm/dL, hemoglobin <10.5 gm/dL, lymphocyte count <1400 or <11% of white blood cell (WBC) count. On multivariate analysis, albumin <3.5gm/dL, lymphocyte count <1400 or <11% of WBC remained significantly associated with relapse, with adjusted HRs of 2.2 (95% CI 1.1-4.5; P<0.03) and 2.6 (95% CI 1.1-6.2; P<0.025), respectively. Hence, a score was constructed using 0, 1 or 2 of these factors. Pts with 0-1 or 2 new risk factors and negative PET-2 had a relapse rate (RR) of 10% and 42%, respectively (HR=4.7; 95% CI 4.7-11), while in pts with positive PET-2 the RR was 30% (Table 1). However, one should bear in mind that pts with IPS 0-2 initiated therapy with ABVDx2 and those with IPS≥3 initiated therapy with EBx2. Conclusions: The current analysis, using data prospectively collected during a phase II study but analyzed retrospectively after pts had been stratified by IPS, suggests a scoring model that could refine the IPS-based identification of pts at a higher risk for disease progression, even if their PET-2 is negative. The findings imply that pts with 2 new risk factors (19% of pts) may need to initiate more intensive therapy than ABVD. However, given the retrospective nature of the analysis, its results should be interpreted with caution. The model needs to be verified in an independent cohort of pts with advanced HL using uniform treatment protocols. Table 1 Table 1. Disclosures Bairey: Janssen: Consultancy.

scholarly journals Should a Bulky Mediastinal Mass ≥7cm in the Longest Dimension be Considered an Adverse Prognostic Factor in Patients with Advanced Hodgkin Lymphoma and Negative Interim PET/CT?

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4051-4051
Author(s):  
Eldad J Dann ◽  
Rebeca Lopez-Alonso ◽  
Shunan Qi ◽  
Tania Mashiach ◽  
Michal Weiler-Sagie ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Hodgkin Lymphoma ◽  
Mediastinal Mass ◽  
Reference Group ◽  
Free Survival ◽  
Adverse Prognostic Factor ◽  
Interim Pet ◽  
Mediastinal Masses ◽  
Pet Ct ◽  
Mass Size

Introduction: Nowadays, treatment decision making in advanced Hodgkin lymphoma (ad-HL) is based on pre-therapy risk factors and interim PET/CT (PET-2) results, used as a platform for therapy modification. In the past, a bulky mediastinal mass (BMM) was not found to be a significant risk factor and was not included in the final version of the International Prognostic Score (IPS) system (Hasenclever, NEJM 1998). The current study aimed to assess the effect of BMM presence on relapse-free survival (RFS) in patients (pts) with ad-HL and to determine the optimal cutoff of the mass size for outcome prediction in the PET/CT era. Methods: The Israeli Hodgkin Lymphoma Study Group selected to initiate therapy with standard BEACOPP (SB: bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) or ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) in HL pts with IPS 0-2 and with intensified therapy using escalated BEACOPP (EB: bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone) in pts with IPS ≥3. Treatment was modified according to PET-2 results. To pts with negative PET-2 another 4 cycles of SB/ABVD were administered. PET-2 positive pts received 4 EB cycles followed by radiation therapy (Dann, Blood 2007). In the present study, disease bulkiness, assessed using baseline PET/CT, was retrospectively evaluated in a cohort of HL pts. The data included measurements of the longest diameter of either the biggest single mass or a conglomerate of lymph node masses in the transverse or coronal plane in the PET/CT image. Prognostic values of mediastinal mass cutoffs of ≥5 cm, ≥7 cm, >10 cm for RFS and progression-free survival (PFS) were compared. Results: One hundred and ninety six pts (female/male: 46/54%) with ad-HL [stage IIB - 28, stage III - 74, stage IV - 94; IPS 0-2 - 104; IPS 3-7 - 92; median age 31 years (16-85)] treated at the Rambam Health Care Campus (n=121) and Memorial Sloan Kettering Cancer Center (n=75) between 2000-2016 were included in the analysis. Mediastinal masses ≥5 cm, ≥7 cm and >10 cm were observed in 125 (63%), 82 (42%), 36 (18%) pts, respectively. PET-2 was negative in 79% of pts. At a median follow-up of 66.5 (1-222) months [80 (4-222) for pts without disease progression and 12 (1-62) for those with relapse or progression], estimated 5-year RFS and PFS for the entire group were 82% and 79%, respectively. A mass of up to 7 cm was found in 62 % of pts (n=123); 22% (n=44) had a mass measuring between 7 and 9.9 cm and 15% (n=29) had a mass ≥10 cm. Mediastinal masses were prevalent in 126/196 (64%) pts; in 58 (30%) of them the mediastinal mass, while being biggest, did not exceed 7 cm, and 68 (34%) had BMM of ≥7 cm. We found no effect of bulky disease, either mediastinal or non-mediastinal, on the outcome of the PET-2 positive group. Univariate analysis showed that in pts with negative PET-2, BMM ≥7 cm was a significant adverse prognostic factor for both 5-year RFS and PFS (HR 2.85; 95% CI 1.09-7.41; p=0.032 and HR 2.86; 95% CI 1.1-7.45; p=0.032, respectively). Outcome comparison of PET-2 negative pts with BMM (≥7 cm) to pts with negative PET-2 and either non-mediastinal or mediastinal non-bulky (<7cm) masses (reference group) revealed an inferior 5-year RFS of 73% versus 89% (HR 2.97; 95% CI 1.37-6.42; p=0.006) in the former group. Of note, both groups received an ABVD/SB regimen. HR for RFS was insignificant when a mass size cutoff of ≥5 cm or >10 cm was used. The HR for RFS was particularly high in the comparison between the subgroup of PET-2 negative pts with IPS 0-2 and BMM (≥7 cm) and those with IPS 0-2 in the reference group, demonstrating a 5-year RFS of 59% versus 89% with HR of 4.20 (95% CI 1.59-11.05; p=0.004). PET-2 negative pts with IPS 3-7 and BMM (≥7 cm) did not have an inferior outcome compared to pts with IPS 3-7 from the reference group (5-year RFS of 82% versus 89%). Notably, the two groups were treated with an EB-containing regimen. Our results indicate that BMM is an important adverse prognostic factor predominantly for pts with IPS 0-2. Multivariate Cox regression analysis identified BMM ≥7 cm as the most significant adverse prognostic factor for RFS (Table 1; Fig. 1). Conclusions: In PET-2 negative pts with ad-HL, mediastinal masses ≥7 cm in any plane are associated with the highest risk for HL progression. These findings should be incorporated in a new prognostic scoring system upon more extensive evaluation in a larger cohort. Disclosures No relevant conflicts of interest to declare.

For Standard and High-Risk Patients with Hodgkin Lymphoma Six Cycles of Tailored BEACOPP, Based On Interim Scintigraphy, Are Effective and Female Fertility Is Preserved.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1552-1552 ◽  
Author(s):  
Eldad Dann ◽  
Rachel Bar-Shalom ◽  
Ada Tamir ◽  
Menachem Ben-Shachar ◽  
Irit Avivi ◽  
...  
Keyword(s):  
High Risk ◽  
Hodgkin Lymphoma ◽  
Young Female ◽  
Prognostic Features ◽  
High Risk Patients ◽  
Female Patients ◽  
Interim Pet ◽  
Pet Ct ◽  
Risk Patients

Abstract Abstract 1552 Poster Board I-575 This prospective study (124 patients) evaluated the outcome of patients with Hodgkin lymphoma (HL) whose therapy was tailored based on results of scans performed after 2 cycles of chemotherapy, thus reducing the dose for early responders and maximizing the dose for those with subptimal early response or progression. The study was initiated in 1999 for patients with HL aged 18-60 years. Eligibility criteria were: unfavorable HL stages I, II and stage III or IV. Disease was defined according to the International Prognostic Score (IPS). Standard risk patients were treated with 2 cycles of standard BEACOPP (SB) and those with IPS of 3 3 got 2 cycles of escalated BEACOPP (EB): Ga67(on 57 patients prior to 2001) or hybrid PET/CT scan (on all 67 since 2001) were performed at diagnosis and after the 1st or 2nd cycle for all 124 patients. If early interim scan remained positive, additional 4 cycles of EB were used; otherwise, SB was given. Data for 108 patients were previously reported (Blood, 2007); albeit with a median follow-up of only 4 years. Herein is an updated 6- year median follow-up for all previously reported patients who had Ga67 or PET/CT as well as 16 additional patients who underwent interim PET/CT. Furthermore, importantly, the fertility of all young female patients is herein reported. For all 124 patients on study, the 7-year event-free survival (EFS) for patients with IPS 0-2 is 89% and for those with IPS of 3 3 87%. Seven year overall survival (OS) is 90%. Sixty seven patients (39 males and 28 females aged 18-55 [median 33]) were treated after 2001 when hybrid FDG-PET/CT became available. Forty one patients had IPS of 0-2 and 26 ≥3. Complete remission (CR) rate was 96%, 5-y FFS and OS were 92% and 97%, respectively at a median follow-up of 56 months (8-90). 5-y EFS and OS were similar for standard and high risk patients. HL progressed in 2/12 patients with interim positive PET/CT versus 3/55 with negative PET (p<0.02) (Table 1). Ninety four percent of patients with negative interim PET/CT had no disease progression during the follow-up, while 17% of patients with interim positive PET/CT progressed. One patient died from breast cancer. Thirty-eight females < 40 years old who had been treated with tailored BEACOPP since 1998 were assessed for fertility status. This is described in Table 2. Twenty six were co-treated with the GnRH agonist triptorelin, concomitantly with chemotherapy. Nineteen conceived during follow-up. Thirteen delivered 17 healthy babies, 6 terminated their pregnancy. Conclusion PET/CT is useful for making an early interim decision about chemotherapy dose on an individual basis, thus reducing unnecessary toxicity and escalating therapy where appropriate based on poor interim prognostic features. The results of 6 cycles of risk-adapted BEACOPP compare favorably with the reported data following 8 cycles of EB. Use of tailored therapy enables reduction of cumulative chemotherapy and preservation of fertility in the majority of young female patients. Disclosures Rowe: Teva Pharmaceuticals: Consultancy; EpiCept Corporation: Consultancy.

scholarly journals 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

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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