scholarly journals Role of Interim PET Scan after 2 Cycles of ABVD in Pediatric Hodgkin Lymphoma: Retrospective Multicenter Study from South India

2021 ◽  
Author(s):  
Arun Seshachalam ◽  
Shashidhar V. Karpurmath ◽  
Krishnakumar Rathnam ◽  
Arathi Srinivasan ◽  
Julius Scott ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
South India ◽  
Tertiary Care ◽  
Stage Iv ◽  
Pet Scan ◽  
Bulky Disease ◽  
Interim Pet ◽  
Pediatric Hodgkin Lymphoma ◽  
Abvd Chemotherapy

Abstract Introduction Most Indian centers use Adriamycin/Bleomycin/Vinblastine/Dacarba-zine (ABVD) chemotherapy for pediatric Hodgkin lymphoma (pHL). To reduce the late toxicity, robust predictive markers are needed to risk stratify pHL patients, thereby limiting the number of chemotherapy cycles and omitting radiation for low-risk and intensifying treatment for high-risk children. Objective This study was conducted to analyze the outcome of pHL patients treated with ABVD and various factors predicting the outcome. Materials and Methods This retrospective study analyzed the outcome of 113 consecutive pHL children treated with ABVD chemotherapy from 11 tertiary care centers in South India from 2009 to 2019. Results The median duration of follow-up was 2.73 years. The median age was 13 years. B symptoms are seen in 50.5% patients, bulky disease in 23%, and stage IV in 28.3%. Of 113 pHL, 69% had a positron emission tomography (PET) and 31% had computed tomography (CT)-based staging. Stage IV (37.1%) and extranodal involvement (31.2%) were seen more often with PET than with CT staging (8.5 and 2.8%, respectively). Among 64 patients with interim PET scan after two cycles (iPET2), 20.3% did not achieve complete remission (CR) and no factors were significantly associated. The 4-year event-free survival (EFS) rate of the entire cohort was 86%. The 4-year EFS rate was 93% for patients with CR in iPET2 and 52% for patients not achieving CR. The only independent predictor of low EFS was iPET2 response (p < 0.05). Conclusion Our study confirms the prognostic role of PET scan staging and response assessment. Not achieving CR on the iPET2 scan indicates poor prognosis and warrants clinical trial enrollment for a better outcome.

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.

scholarly journals Does Interim PET Scan After 2 Cycles of ABVD Predict Outcome in Hodgkin Lymphoma? Real-World Evidence

2019 ◽  
pp. 1-13 ◽  
Author(s):  
Arun Seshachalam ◽  
Shashidhar V. Karpurmath ◽  
Krishnakumar Rathnam ◽  
S. Ganapathi Raman ◽  
Murugesan Janarthinakani ◽  
...  
Keyword(s):  
High Risk ◽  
Hodgkin Lymphoma ◽  
Tertiary Care ◽  
Stage Iv ◽  
Secondary Data ◽  
Response Assessment ◽  
Complete Response ◽  
Female Ratio ◽  
Entire Cohort ◽  
Interim Pet

PURPOSE Escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) improves overall survival (OS) in patients with Hodgkin lymphoma (HL) relative to ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) therapy. However, the associated higher cost and toxicity discourage clinicians from prescribing it. Identifying high-risk patients and administering escalated BEACOPP remains an effective strategy. We assessed the significance of interim positron emission tomography (iPET) scan after 2 cycles (iPET2) in identifying this high-risk subset. PATIENTS AND METHODS This cohort study used secondary data from 12 tertiary care centers in South India gathered over 10 years (2008-2018). OS, event-free survival (EFS), determinants of EFS, and complete response (CR) in iPET2 were assessed. RESULTS The study included 409 patients with HL (mean age, 34.5 years; male/female ratio, 1.4:1). The median duration of follow-up was 2.8 years. Of 409 patients, 63% underwent PET-based staging and 37% underwent computerized tomography (CT) staging. Stage IV (28.9%) and bone involvement (9.2%) were seen more often with PET than with CT staging (9.2% and 2%, respectively). Among 171 patients with iPET2 results, 24% did not achieve CR, and no factors were significantly associated. The 5-year EFS and OS rates of the entire cohort were 78% and 97%, respectively. The 5-year EFS and OS rates of patients with CR on iPET2 were 90% and 99%, respectively, whereas these were 65% and 100%, respectively, for patients not achieving CR. On univariable analysis, sex, stage, and iPET2 response significantly predicted inferior EFS. On multivariate analysis, only iPET2 response significantly predicted EFS ( P < .000). CONCLUSION Our study supports the use of PET for staging and iPET2 for response assessment. Nonachievement of CR on iPET2 indicates unfavorable outcome, and such patients may benefit from more intensive treatment.

FDG-PET Guided Consolidative Radiotherapy in Patients with Advanced Stage Hodgkin Lymphoma with Residual Abnormalities on Post Chemotherapy CT Scan.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 213-213 ◽  
Author(s):  
Kerry J. Savage ◽  
Joseph M. Connors ◽  
Don Wilson ◽  
Richard Klasa ◽  
Tamara Shenkier ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Fdg Pet ◽  
Ct Imaging ◽  
Pet Scan ◽  
Stage Iii ◽  
Advanced Stage ◽  
Bulky Disease ◽  
Residual Mass ◽  
Consolidative Radiotherapy

Abstract Consolidative radiotherapy (RT) is often administered following chemotherapy for advanced stage Hodgkin lymphoma (HL) with bulky disease at diagnosis or for residual abnormalities on post-chemotherapy CT imaging. It is unknown whether RT is necessary for such patients if the residual mass is FDG-PET-negative (PET-neg) following chemotherapy (CHT). Further, it has been previously shown that a post-therapy PET-positive (PET-pos) scan is highly predictive of future relapse; however, it is unclear whether consolidative RT can be used to salvage these cases. Methods Since July 2005, adult (&gt; 16 y) patients in British Columbia (BC) with advanced stage HL (stage III /IV and/or the presence B symptoms and/or bulky disease (&gt; 10cm)) have been treated with 6 cycles with ABVD followed by a PET scan for further treatment planning if residual abnormalities ≥2 cm were observed on CT imaging. Prior to this, post-treatment PET scans were obtained in some individuals by self-pay. If the PET scan was positive, RT was administered if feasible, otherwise, patients were observed. There were 68 eligible patients, including 7 self-pay patients, that were identified in the BC Lymphoid Cancer Database. 16 patients were excluded (PET not performed (5); palliative tx or refusal (3); composite lymphoma (1); progressive disease during CHT or at the time of PET scan (4); HIV + (1); PET mid-therapy (1); death due to unrelated cause prior to PET scan (n=1).), leaving a total of 52 patients who had a PET scan post-chemotherapy for a residual mass and who had adequate follow-up (median 19 m, 10–59 m). Patient characteristics include: M:F 1.1:1, Median age 29 (17–81); 55% stage II, 46% stage III/IV 44%; 49% bulky disease; 69% B symptoms; IPFP Prognostic score 0 8%; 1 39%; 2 26%; &gt;3 26%. Results In total, 40/52 (77%) were PET-neg and 12/52 (23%) were PET-pos (SUV mean 4.4, 2.2–6.8). PET-pos patients had an inferior 2 y PFS compared to PET-neg patients (26% vs 91%, p=.001). In the PET-pos group, 10/12 received the planned RT and 5 have relapsed. In the PET-neg group, there was no difference in the 2 y PFS in patients with bulky (n=17) vs non-bulky disease (n=20) (86% vs 94%, p=.35). Conclusions Advanced stage HL patients who achieve a post-CHT PET-neg status are at a low risk of relapse and do not require additional consolidative RT thus avoiding potential long-term side effects. The majority of patients with bulky disease who have a PET-neg scan following CHT also remain in remission, however, longer follow-up is still needed. Although some patients with a positive PET-scan may be salvaged by consolidative RT, a high proportion ultimately relapse. Figure Figure Figure Figure

BEACOPP Chemotherapy Is Able to Induce Durable Complete Remission in Poor-Prognosis Hodgkin’s Lymphoma Patients with a Positive Interim PET after 2 ABVD Cycles

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2594-2594
Author(s):  
Andrea Gallamini ◽  
Alessandro Rambaldi ◽  
Alberto Biggi ◽  
Silvia Tavera ◽  
Caterina Patti ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Poor Prognosis ◽  
Univariate Analysis ◽  
Pet Scan ◽  
Advanced Stage ◽  
Bulky Disease ◽  
Interim Pet ◽  
Number Of Patients ◽  
The Mean

Abstract Background: Early interim-PET (PET-2) is the most powerful factor able to predict treatment outcome in advanced-stage Hodgkin Lymphoma (HL) patients treated with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine). The 2-y PFS of PET-2 positive patients is only 12%, but the optimal treatment for this patient subset is still unknown. For this reason in January 2006 a treatment policy was designed by GITIL (Gruppo Italiano Terapie Innovative nei Linfomi) to early intensify chemotherapy with BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) for HL patients with a PET-2 positive after 2 ABVD cycles. Patients and methods: 136 HL patients with advanced-stage or intermediate-stage with adverse prognostic factors (more than 3 nodal sites, ESR &gt; 50 mm, sub diaphragmatic presentation, bulky lesion), consecutively admitted to nine GITIL Italian centers were treated with two ABVD courses and re-evaluated with interim-PET. Twenty-one of these 136 patients proved to be PET-2 positive, and 19/21 are the object of this analysis. The mean age was 31.7 years (16–64), 10 patients were in stage II, 9 in stage III–IV. Bulky disease was present in 11, and B-symptoms in 16. Fourteen patients showed an IPS score 0–2, 5 patients a score 3–7. The median interval between the end of second ABVD course and PET-2 was 11 days (5–14). BEACOPP (4 escalated and 4 standard cycles) was followed by consolidation radiotherapy in 3 patients for bulky mediastinal tumor. PET scan were centrally reviewed by two well-experienced nuclear medicine experts, using the blood pool mediastinal structures (BPMS) as reference for the residual uptake, as elsewhere published (Gallamini, JCO 2007). Results. Upon central review, 2 interim-PET scan were classified as minimally positive in 2 patients, with a single MRU (Minimal Residual Uptake) lesion showing a SUV (Standardized Uptake Value) lower than BPMS, and therefore only 19 cases were suitable for the BEACOPP salvage treatment. After a mean follow-up of 14.3 months (7.0–30.2), 15 patients remain in continuous CR and 4 had a treatment failure because of disease relapse (1) or progression (3). For the responding patients the mean duration of CR was 13.0 months (6.5–30.2). The IPS score for progressing patients was 2, 3, and 4; for the relapsing-one, 0. At time of this analysis, l8 patients are still alive and 1 died during BEACOPP treatment for disease progression. The 1-year second treatment failure-free survival (1-y 2TFFS) was 94.7 % (95% C.I. 84.7–100). The 1 y OS survival was 93.3 (95%C.I. 80.7–100). In univariate analysis the only clinical factor related to treatment failure was the presence of extra-nodal disease. (Log-rank=6.8 p=0.009). Conclusions. BEACOPP-escalated regimen was able to induce durable CR in most (15/19) HL patients with a positive interim-PET. These results, although requiring a longer follow-up and a higher number of patients, seem to suggest that the very-poor prognosis of PET-2 positive, ABVD-treated HL patients can be substantially improved by early chemotherapy intensification; escalated-BEACOPP is likely to represent a good treatment choice for this very poor prognosis patient subset.

Comparative Assessment of Different Criteria for Interim-PET Interpretation in a Cohort of Hodgkin Lymphoma Patients Treated in a Single Center.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3657-3657
Author(s):  
Andrea Gallamini ◽  
Stephane Chauvie ◽  
Francesca Fiore ◽  
Roberto Sorasio ◽  
Flavia Salvi ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Hodgkin Lymphoma ◽  
Conflicts Of Interest ◽  
Prognostic Score ◽  
Advanced Stage ◽  
Dimensional Approach ◽  
Treatment Change ◽  
Bulky Disease ◽  
Fdg Uptake ◽  
Interim Pet

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.

Interim Absolute Lymphocyte Count (ALC) As a Predictor of Survival in Hodgkin Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2640-2640
Author(s):  
Tarsheen K. Sethi ◽  
Van T Nguyen ◽  
David S Morgan ◽  
John P. Greer ◽  
Nishitha M Reddy
Keyword(s):  
Overall Survival ◽  
Hodgkin Lymphoma ◽  
Lymphocyte Count ◽  
Absolute Lymphocyte Count ◽  
Disease Stage ◽  
Predictive Score ◽  
Advanced Stage ◽  
Bulky Disease ◽  
Nodular Sclerosis

Abstract Introduction: Patients with Hodgkin lymphoma (HL) have excellent response to current chemotherapy, however, up to 20% may have relapsed/refractory disease. Lymphocytopenia at diagnosis has been found to be predictive of survival in patients with advanced stage HL. An ALC of <600/μlat diagnosis as part of the Hasenclever predictive score is associated with a poorer prognosis. Furthermore, lymphocyte count at the time of apheresis and at day 15 after autologous SCT has been found to be predictive of survival in patients of HL. ALC is considered a surrogate indicator for the tumor microenvironment as well as immune recovery post treatment. There are no large studies evaluating the clinical significance of ALC recovery in patients with HL during initial chemotherapy treatment. In this study, we evaluated the role of lymphocyte recovery during and after standard chemotherapy in patients with HL. Patients and Methods: We analyzed 183 patients with Classical Hodgkin lymphoma treated at our institution between 1996 and 2014 following IRB approval. Complete data was available for 115 patients. We evaluated the absolute lymphocyte count at diagnosis, interim staging (after 2 cycles, Òinterim ALCÓ), at time of completion of chemotherapy and at 6 weeks and 3 months post completion of chemotherapy. Patients were categorized into two groups based on ALC where lymphocytopenia was defined as an ALC of <1x103/µl for adults based on standard criteria. Differences between the two groups were analyzed using Chi- square and t -Student tests. Statistical significance was set at P <0.05. Kaplan Meier method was used to calculate the Progression-free survival (PFS) and overall survival (OS). Log-rank test was used to determine the differences in survival. Statistical analysis was performed using SPSS.22 software. Results: The median age of patients was 31 years (yrs.) (range: 17-76 yrs.) and 53% of patients were male. 100% patients had an ECOG status of 0-1. 48% patients presented with B symptoms, 42% had advanced stage disease (Stage III and IV) and 22% had bulky disease (defined as a mass > 10 cm or mediastinal mass >1/3 of diameter of thorax at T5-T6). In terms of histology, 68% patients had classical nodular sclerosis HL, 19% syncytial variant of nodular sclerosis HL, 8% mixed cellularity HL and 5% Classical HL (NOS). 90% patients received ABVD as their initial chemotherapy, 2% received Stanford V and 1% received MOPP. The remaining patients were treated on a clinical trial. In the analysis of the 115 patients for whom the lymphocyte data was available, at a median follow up of 40 months, 57% in the ALC <1x103/µl group versus 66% in the ALC >1x103/µlgroup had not progressed. The median overall survival was not reached in the two groups. In the multivariate analysis, for PFS, interim ALC predicted survival independent of the interim staging response. The ALC at the time of interim staging scan (interim ALC) was associated with a significantly superior PFS in the group with ALC>1x103/µl(HR=4.16, 95% CI 2.37 to 7.28, P=0.024). There was no difference in overall survival between the groups (Fig. 1&2,P=0.28). For ALC at other time points, no statistically significant differences in PFS or OS were found in the two groups based on ALC at diagnosis, completion of therapy, six weeks and three months post therapy. Discussion: In summary, our results suggest that for patients across all stages and histopathologic subtypes of classical HL receiving first line chemotherapy, interim ALC >1x103/µl (after 2 cycles) is associated with a superior PFS as compared with ALC <1 x103/µl and this is independent of the interim staging response. This did not translate into a difference in OS. Further studies are underway to determine the role of immune effector cells in the context of newer therapeutic agents. Figure 1. PFS (months) in patients with interim ALC >1x103/ μlvs. <1x103/ μl Figure 1. PFS (months) in patients with interim ALC >1x103/ μlvs. <1x103/ μl Figure 2. OS (months) in patients with interim ALC >1x103/ μlvs. <1x103/ μl Figure 2. OS (months) in patients with interim ALC >1x103/ μlvs. <1x103/ μl Disclosures Reddy: Gilead: Other: Speaker; Seattle Genetics: Consultancy; ImmunoGen: Consultancy; PCYC: Consultancy; Celgene: Consultancy, Research Funding.

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