Childhood Hodgkin International Prognostic Score (CHIPS) and Interim PET can Predict Event-Free Survival In Hodgkin Lymphoma

2019 ◽  
Vol 19 ◽  
pp. S311
Author(s):  
Reham Khedr ◽  
Sally Mahfouz ◽  
Huda Fathy ◽  
Lobna Shalaby
2016 ◽  
Vol 64 (4) ◽  
pp. e26278 ◽  
Author(s):  
Cindy L. Schwartz ◽  
Lu Chen ◽  
Kathleen McCarten ◽  
Suzanne Wolden ◽  
Louis S. Constine ◽  
...  

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3649-3649 ◽  
Author(s):  
Cindy Schwartz ◽  
Lu Chen ◽  
Louis Constine ◽  
Suzanne Wolden ◽  
Frank G Keller ◽  
...  

Abstract Abstract 3649 Purpose: To develop a method for predicting Event Free Survival (EFS) in Hodgkin Lymphoma (HL) using clinical factors known at diagnosis. Background: Although early response as measured by CT and/or PET scan has proven useful in the allocation of patients to therapy (eg. eliminating radiation or augmenting chemotherapy) (D Friedman, ASH 2010), stratification at diagnosis may allow earlier modification of treatment approach. The International Prognostic Score (D. Hasenclever, N Engl J Med, 1998) has been used effectively in adults with advanced stage disease, but includes predictors that may not be applicable to the pediatric and adolescent population. 1721 patients with intermediate risk HL (excludes IA and IIA without bulk disease and IIIB/IVB) were treated on AHOD0031, a Children's Oncology Group study using a dose dense, response based algorithm. 770 patients who were randomized or assigned to receive the same treatment (4 ABVE-PC and IFRT) serve as the basis for this report. Methods: Patients <21 years with intermediate risk HL were eligible for COG AHOD0031. The study evaluated the tailoring of treatment by early response to 2 ABVE-PC. Rapid early response (RER) was a 2-dimensional tumor reduction of >60% after 2 cycles of ABVE-PC. Complete response (CR) was a >80% 2-diminsional reduction by CT, and resolution of nuclear imaging abnormalities. RER who achieved CR after 2 additional ABVE-PC were randomized to +/− 21Gy. Slow early responders (SER) were randomized to +/− DECA in addition to the 4 ABVE-PC/21 Gy. Cox regression analysis was used to evaluate potential predictors of EFS (gender, age, race, stage, mediastinal mass, B symptoms, hemoglobin, sedimentation rate, albumen, histology). Continuous variables were dichotomized by clinical significance or quartiles of the population. Multivariable predictive modeling was performed using univariate predictors with a p<0.25. In instances of collinearity, the most robust variable was used. A stepwise selection algorithm was used to identify predictors with a p<0.15. Results: Four predictors (stage 4, large mediastinal adenopathy, albumen<3.5 and fever) were identified as predictive of adverse EFS. Since the Hazard Ratios were similar, the CHIPS (Childhood Hodgkin IPS) score was devised that gave 1 point for each of the 4 adverse predictors. EFS based on score was found to predict an excellent outcome of nearly 90% for those with CHIPS 0 or 1 (N=589) vs. 78% or 62% for those with CHIPS 2 or 3 respectively (N= 141 and 32). Conclusion: The CHIPS score identifies a subset of patients accounting for 22% of an intermediate risk population who are predicted to have an EFS <80%. Early augmentation of therapy may improve outcome for this cohort. After further validation of this approach in historical cohorts, future studies will evaluate the utility of the CHIPS in additional cohorts of newly diagnosed patients. Disclosures: No relevant conflicts of interest to declare.


2014 ◽  
Vol 6 (1) ◽  
pp. e2014063 ◽  
Author(s):  
Eldad J Dann

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.  


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 215-215 ◽  
Author(s):  
Amanda R. Wedgwood ◽  
Michelle A. Fanale ◽  
Luis E. Fayad ◽  
Peter McLaughlin ◽  
Fredrick B. Hagemeister ◽  
...  

Abstract The use of rituximab in classical Hodgkin lymphoma (HL) has been proposed to have a therapeutic value by several mechanisms; to The malignant Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin lymphoma (HL) rarely survive outside their microenvironment of reactive B-cells, and therefore we hypothesized that depleting B-cells from HL microenvironment by rituximab may deprive HRS cells from critical survival and resistance factors and therefore improving the efficacy of chemotherapy, Rituximab may have a direct killing effect on HRS cells that express CD20, and recent data from Johns Hopkins Medical Center suggested that HRS stem cells are CD20+ cells. With this background, we evaluated the safety and efficacy the combination of rituximab and ABVD (R-ABVD) chemotherapy in newly diagnosed patients with classical HL. In addition, PET after 2–3 cycles of ABVD has been shown to confer poor prognosis and therefore proposed to guide future therapy. (Hutchings et al, Blood, 2006) reported a negative PET scan after two cycles of ABVD to be a good predictor of outcome with 96% 2-year progression free survival (PFS). Those with PET positive after 2 cycles had a 0% PFS at 2 years. Thus, we examined the effect of RABVD on early PET imaging and determined whether PET status remains predictive of treatment outcome in patients receiving RABVD. To date 70 newly diagnosed pts are enrolled, of whom 65 pts had at least 12 months of follow up and are evaluable for treatment response. Median age 28 years (Range; 18–72 years). Patients had stage II (50%), stage III (31%), stage IV (19%) disease. Using the IPS prognostic score model, 36 patients (55%) had a score of 2 or higher. With a median follow up of 32 months, the estimated event-free survival (EFS) is for the entire group is 85% and overall survival 98%. EFS for patients with IPS 0–1, 2, and &gt;2 are 95%, 76%, and 77%, respectively, suggesting that R-ABVD improved EFS in all IPS scores with the biggest impact seen in patients with IPS &gt; 2. 55 patients had PET after 2–3 cycles and were included in the predictive analysis of PET on treatment outcome. PET became negative in 43 patients (78%) after completing 2–3 cycles of RABVD and positive in the remaining 12 patients (22%). 5-year EFS for those with negative PET was 93% and 75% for those who remained PET positive (p=0.05). We conclude that in patients with classical HL, the addition of 6 weekly doses of rituximab to standard dose and schedule of ABVD chemotherapy is effective in terms of remission rate and remission duration irrespective of IPS category. Our data confirmed prior reports that patients who remain PET positive after 2–3 cycles have worse prognosis when compared to those that achieve PET negativity. However, the outcome for those who remained PET positive after 2–3 cycles of RABVD seems to be significantly better than what has been previously reported when using ABVD alone. A randomized trial comparing ABVD with RABVD is planned to confirm these observations.


2016 ◽  
Vol 57 (8) ◽  
pp. 1839-1847 ◽  
Author(s):  
Ljubomir R. Jakovic ◽  
Biljana S. Mihaljevic ◽  
Bosko M. Andjelic ◽  
Andrija D. Bogdanovic ◽  
Maja D. Perunicic Jovanovic ◽  
...  

2018 ◽  
Vol 36 (20) ◽  
pp. 2024-2034 ◽  
Author(s):  
Ulrich Dührsen ◽  
Stefan Müller ◽  
Bernd Hertenstein ◽  
Henrike Thomssen ◽  
Jörg Kotzerke ◽  
...  

Purpose Interim positron emission tomography (PET) using the tracer, [18F]fluorodeoxyglucose, may predict outcomes in patients with aggressive non-Hodgkin lymphomas. We assessed whether PET can guide therapy in patients who are treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Patients and Methods Newly diagnosed patients received two cycles of CHOP—plus rituximab (R-CHOP) in CD20-positive lymphomas—followed by a PET scan that was evaluated using the ΔSUVmax method. PET-positive patients were randomly assigned to receive six additional cycles of R-CHOP or six blocks of an intensive Burkitt’s lymphoma protocol. PET-negative patients with CD20-positive lymphomas were randomly assigned or allocated to receive four additional cycles of R-CHOP or the same treatment with two additional doses rituximab. The primary end point was event-free survival time as assessed by log-rank test. Results Interim PET was positive in 108 (12.5%) and negative in 754 (87.5%) of 862 patients treated, with statistically significant differences in event-free survival and overall survival. Among PET-positive patients, 52 were randomly assigned to R-CHOP and 56 to the Burkitt protocol, with 2-year event-free survival rates of 42.0% (95% CI, 28.2% to 55.2%) and 31.6% (95% CI, 19.3% to 44.6%), respectively (hazard ratio, 1.501 [95% CI, 0.896 to 2.514]; P = .1229). The Burkitt protocol produced significantly more toxicity. Of 754 PET-negative patients, 255 underwent random assignment (129 to R-CHOP and 126 to R-CHOP with additional rituximab). Event-free survival rates were 76.4% (95% CI, 68.0% to 82.8%) and 73.5% (95% CI, 64.8% to 80.4%), respectively (hazard ratio, 1.048 [95% CI, 0.684 to 1.606]; P = .8305). Outcome prediction by PET was independent of the International Prognostic Index. Results in diffuse large B-cell lymphoma were similar to those in the total group. Conclusion Interim PET predicted survival in patients with aggressive lymphomas treated with R-CHOP. PET-based treatment intensification did not improve outcome.


2010 ◽  
Vol 51 (9) ◽  
pp. 1337-1343 ◽  
Author(s):  
J. J. Cerci ◽  
L. F. Pracchia ◽  
C. C. G. Linardi ◽  
F. A. Pitella ◽  
D. Delbeke ◽  
...  

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3657-3657
Author(s):  
Andrea Gallamini ◽  
Stephane Chauvie ◽  
Francesca Fiore ◽  
Roberto Sorasio ◽  
Flavia Salvi ◽  
...  

Abstract Abstract 3657 Poster Board III-593 Introduction Interim-PET scan performed early during treatment is the most important prognostic factor in Hodgkin lymphoma (HL). However, simple reproducible criteria for scan interpretation are lacking and still await standardization. Aim of the study To evaluate in a cohort of ABVD-treated HL patients in a single centre the overall accuracy of different criteria of interim PET interpretation in which interim scan was not decisional for treatment change. Patients and methods From December 2003 till June 2008, 75 HL patients were consecutively admitted to hematology department of Santa Croce Hospital in Cuneo. Baseline and interim-PET (PET-2) scans were performed with a PET/CT equipment. Limited-stage patients (I-IIA) were treated with ABVD x 3-4 plus Involved-field radiotherapy; advanced-stage (IIB-IVB) patients with ABVD x 6 plus consolidation radiotherapy on bulky disease. The injected dose was 370 MBq/70 kg. 2D images were acquired a mean of 71 (47-122) minutes after Fluorodeoxyglucose (FDG) injection. Images were reconstructed with OSEM (3 iteration, 26 subsets). PET-2 was performed after a median of 11(8-13) days from 2nd ABVD end, and no treatment change was allowed based on PET-2 results. Two expert nuclear medicine physicians independently interpreted the PET-2 scans and jointly reviewed the discordant cases. Six interpretation criteria on the basis of literature reports were used: three qualitative, two quantitative, based on Standardized Uptake Value (SUV) assessment, and one with a qualitative/dimensional approach, with a dimensional cutoff value for FDG correction of 15 mm.: Juweid 2007 (Ju), Gallamini 2007 (Ga), Barrington 2008 (Ba) for qualitative, SUVmax determination, SUVmax variation (deltaSUV) for quantitative, and Barrington + dimensional (Ba/d) for a qualitative/dimensional approach. Results Clinical characteristics of the patients were: mean age 33 (14 - 73), male sex 39/75, limited vs. advanced stage 37/38, International Prognostic Score (IPS), (in 69/75 patients) was 0 in 17,1 in 19, 2 in 19, 3 in 8, 4 in 5, 5-7 in 1 patients. After a mean follow-up of 937 days 67 patients are in CR, and 8 experienced treatment failure, three of them have died. In case of residual FDG uptake the mean diameter of the persisting lesion was 19.9 mm. Overall, 2/8 patients with treatment failure (True PET-2+) and all the 9 patients with false+ or false- PET-2 (whatever criteria) showed a persistent FDG uptake in a single lesion, with a median diameter of 14 millimetres. Sensitivity and specificity, were:100%,70%, for Ju; 63%, 87% for Ga; 63%, 91% for Ba; 75%, 93% for SUVmax; 50%, 94% for deltaSUV; 89%, 89% for Ba/d. Among the qualitative assays Ba and Ba/d showed the best results. The latter were equivalent to both quantitative assay. Using the Ba /d score 8 patients showed false-positive scans: 6/8 with stage IIA and 7/8 with bulky disease, and the 3-year failure-free survival for the entire cohort and for advanced-stage patients were 98%, 53% and 96% and 25% for PET-2 negative and positive patients, respectively. Conclusions This study suggest that (1) the criteria of the Harmonization Study for end-treatment evaluation of response should not be used for PET-2 interpretation (2) the lower performance of qualitative in respect to the quantitative criteria is offset by the adjunction of dimensional parameters; (3) due to the small size of the residual lesion with a persistent FDG avidity in PET-2, the contribute of the dimensional criteria could sensibly improve the performance of qualitative criteria, such as Ba, that are currently used for multicenter clinical trials. Disclosures: No relevant conflicts of interest to declare.


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