Interim Positron Emission Tomography Scan Research Articles

PET4 Response As an Independent Predictor of Long-Term Outcomes in ECHELON2 (A+CHP Vs. CHOP) in CD30+PTCL

Background: Peripheral T-cell lymphomas (PTCLs) are uncommon, heterogeneous, and often aggressive subtypes of lymphoma characterized by a high risk of progression even after combination chemotherapy. The phase III, ECHELON-2 trial showed that the combination of brentuximab vedotin with chemotherapy (A+CHP) in patients (pts) with CD30-positive PTCLs improved progression-free survival (PFS) and overall survival (OS) compared to CHOP. In PTCL, positron emission tomography (PET) is a valuable way to assess disease burden and stage at the time of diagnosis and evaluate treatment response. Prior retrospective studies have shown that interim and end of treatment PET may predict outcomes; however, there are no prospective studies confirming their predictive value. In the ECHELON-2 study, PET4 outcomes were prospectively collected, and the objective of this exploratory analysis is to investigate the potential for interim PET scans to predict treatment response and long-term outcomes. Objective: To evaluate the role of interim 18F-FDG PET imaging (PET4) in predicting end of treatment (EOT) response, progression free survival (PFS), and overall survival (OS) in pts (pts) with CD30+PTCL treated with A+CHP or CHOP in the ECHELON-2 trial. Methods: The ECHELON-2 trial included prospective 18F-FDG PET scans and assessment of treatment response including long-term PFS per investigator and OS. PET4 status was based on Deauville score by Independent Review Facility (IRF) assessment using scans at the cycle 4 response assessment. Deauville scores 1-3 are considered negative (PET4neg) and 4-5 positive (PET4pos). EOT response is the best response after completion of study treatment and prior to long term follow up per Cheson 2007 by IRF assessment. Kaplan-Meier methods were used to estimate PFS and OS; p-values are based on stratified log-rank tests. All analyses are exploratory, and p-values are descriptive. Results: In this study, 452 pts were included, with 226 randomized to the A+CHP treatment arm and 226 to the CHOP treatment arm; median follow up was 66.8 months (range 0-90). Of randomized pts, 32 pts in the A+CHP arm and 41 pts in the CHOP arm were not evaluable for PET4. The overall results showed that the PET4neg evaluable subgroup had a higher proportion of pts achieving complete responses (CR) than PET4pos (80% vs. 9%) at EOT (Table 1). In pts assessed for PET4, pts who were PET4neg had improved PFS and OS in both the A+CHP and CHOP treatment arms (Figure 1). For A+CHP pts, those who achieved PET4neg had an improved PFS [HR 0.36, CI-95 (0.19-0.66), p=0.0006] and OS [HR 0.38, CI-95 (0.18-0.78), p=0.0060] compared to those who were PET4pos. Similarly, pts in the CHOP arm who achieved PET4neg had an improved PFS [HR 0.26, CI-95 (0.17-0.41), p<0.0001] and OS [HR 0.24, CI-95 (0.14-0.41), p< 0.0001] compared to those who were PET4pos. Among pts with anaplastic large cell lymphoma (sALCL) (n=316), 19 pts in the A+CHP arm and 32 in the CHOP arm were not evaluable for PET4. The results in this subgroup show that 128/143 (90%) A+CHP pts who had PET4 assessments achieved PET4neg. These pts experienced improved PFS [HR 0.28, CI-95 (0.14-0.60), p=0.0004] and OS [HR 0.38, CI-95 (0.16-0.94), p 0.0292] compared to PET4pos pts. For CHOP pts who had PET4 assessments 98/122 (80%), achieved PET4neg; these pts experienced improved PFS [HR 0.31, CI-95 (0.12-0.55), p<0.0001] and improved OS [HR 0.25, CI-95 (0.12-0.25), p= 0.0002] compared to PET4pos pts. Conclusion: In an exploratory analysis of interim PET imaging as part of the ECHELON-2 study, PET4neg by Deauville was associated with improved PFS and OS in both the A+CHP and CHOP arms. Our findings support the use of PET4 response in PTCL as a predictor of outcomes in both the A+CHP and CHOP pts. These findings emphasize the potential of PET scans to enhance risk stratification, individualize therapy decisions, and improve pt outcomes in the management of PTCLs. Further analysis will be presented at the meeting.

Consolidative Autotransplantation Achieves High Cure Rates in Adverse-Risk Large B Cell Lymphoma

There remains an unmet need to optimize the first-line treatment of patients with high-risk large B cell lymphoma (LBCL), particularly those with a high International Prognostic Index (IPI) score or a positive interim positron emission tomography (PET) scan who experience poor outcomes with R-CHOP. This study was conducted to evaluate the real-world effectiveness of consolidative autologous stem cell transplantation (ASCT) among patients with high-risk LBCL. This retrospective study included consecutive patients with LBCL and IPI score 4 or 5 who underwent consolidative ASCT as part of first-line therapy in Alberta, Canada. Progression-free survival (PFS), overall survival (OS), and disease-specific survival (DSS) were determined using the Kaplan-Meier method. The study cohort comprised 114 patients with median age of 60 years (range, 18 to 73 years), of whom 81 (71%) had an IPI score of 4 and 33 (29%) had an IPI score of 5. With a median follow-up of 5.6 years, the 5-year PFS was 72% (95% confidence interval [CI], 62% to 79%), 5-year OS was 74% (95% CI, 64% to 81%), and 5-year DSS was 80% (95% CI, 71% to 87%). There was no significant difference in PFS among patients with and patients without positive interim PET scans (n = 24), MYC and BCL2 and/or BCL6 rearrangements (n = 26), or central nervous system involvement (n = 15). Consolidative ASCT is associated with high cure rates and favorable survival outcomes in patients with high-risk LBCL and may overcome the adverse prognostic impact of a positive interim PET scan.

Interim PET-Guided ABVD or ABVD/Escalated BEACOPP for Newly Diagnosed Advanced-Stage Classic Hodgkin Lymphoma (JCOG1305, INNOVATE-HL study)

Introduction Interim positron-emission tomography (PET) can predict clinical outcomes in patients with classic Hodgkin lymphoma (cHL). The objective of this single-arm confirmatory study (JCOG1305, INNOVATE-HL) is to establish interim PET-guided treatment strategy for newly diagnosed advanced-stage cHL. Methods Patients aged 16-60 years with cHL received 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) as an induction chemotherapy, and then underwent an interim PET scan. Images were centrally reviewed with the use of a 5-point scale for PET findings for further response guided treatments. Patients with negative interim PET findings (defined as score 1 to 3) continued additional 4 cycles of ABVD, whereas those with positive interim PET findings (score 4 or 5) switched to 6 cycles of escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisolone). Involved site radiation therapy (ISRT) was set as a protocol treatment if patients with partial response had a single residual lesion after completion of chemotherapy. The primary endpoint were 2-year progression-free survival (PFS) among all eligible patients and among interim PET-positive patients (co-primary endpoints). We had the following hypotheses: 2-year PFS of eligible patients and interim-PET positive patients will exceed 75% and 35%, respectively, compared to a historical control with one-sided alpha of 0.1. Secondary endpoints included overall survival (OS), event-free survival (EFS), in which events were defined as death, progression or not achieving complete response at end of protocol treatment, and incidences of adverse events and secondary malignancy. This study was registered at jRCTs031180218. Results A total of 93 patients were enrolled from 35 institutions between January 2016 and December 2019. One patient was ineligible because of diagnostic error. Baseline characteristics of 92 eligible patients who underwent an interim PET scan were as follows: a median age of 35 years (interquartile range [IQR]: 28-48); 58% were male; most of patients (87 [95%]) had performance status of 0 or 1; Ann Arbor stage III and IV consisted of 40 (43%) and 43 (47%), respectively, the remaining 9 (10%) had stage IIB with bulky (10 cm or more) mediastinal lesion or nodal lesion involving directly to extranodal lesion; 51 (55%) and 15(16%) had B symptoms and bulky lesions, respectively. An interim PET scan showed 19 patients (21%) with positive findings; those patients received escalated BEACOPP; 18 completed 6 cycles of BEACOPP including one who underwent ISRT, the remaining one discontinued BEACOPP. On the other hand, 73 patients (79%) who had interim PET-negative findings continued ABVD; 70 completed additional 4 cycles of ABVD including two who underwent ISRT, the remaining 3 discontinued ABVD. Average relative dose intensity of induction ABVD, additional ABVD and escalated BEACOPP were 98.6% (±4.0), 96.7% (±5.7) and 82.2% (±9.3%), respectively. With a median follow-up of 41.1 months (IQR: 29.7-53.1), the 2-year PFS were 84.8% (80% confidence interval [CI]: 79.2-88.9) and 84.2% (80% CI: 69.7-92.1) among all 92 eligible patients and 19 interim PET-positive patients, respectively (Figure 1). The 2-year EFS were 76.1% and 68.4% among all eligible patients and interim-PET positive patients, respectively. Bleomycin lung toxicity (BLT) occurred in 9 patients, but no patients led to BLT-related death. Twelve and three patients underwent autologous and allogeneic hematopoietic stem cell transplantation (HSCT) as a salvage treatment, respectively, including one received allogeneic HSCT for relapse after autologous HSCT. The 2-year OS was 98.9%; two patients died due to interstitial pneumonia after autologous HSCT and brain hemorrhage without relapsing cHL among the interim PET-positive patients, whereas no patients died among interim PET-negative patients. Diffuse large B-cell lymphoma developed in one patient with interim PET-negative findings as a secondary malignancy 4.6 years after enrollment. Conclusions This INNOVATE-HL study demonstrated that interim PET-guided treatment strategy was useful for younger patients with newly diagnosed advanced-stage cHL. Of note, 6 cycles of escalated BEACOPP is a feasible and effective regimen for interim PET-positive cHL patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

HL-147: Brentuximab Vedotin with Chemotherapy for Patients with Previously Untreated Stage III/IV Classical Hodgkin Lymphoma: 5-Year Update of the ECHELON-1 Study

<h3>Objective</h3> Historically, nearly all relapses in classical Hodgkin lymphoma (cHL) occur within the first 5 years of treatment (Radford et al., BMJ 1997;314:346). In ECHELON-1, brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) significantly improved modified progression-free survival (PFS) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in patients with stage III/IV cHL (Connors <i>et al.,</i> NEJM 2018;378:331). We report updated efficacy and safety results; median follow-up was 60.9 months. <h3>Design</h3> This phase 3, open-label study (NCT01712490) randomized patients with previously untreated stage III/IV cHL to receive 6 cycles of A+AVD or ABVD. Patients underwent an interim positron emission tomography scan after cycle 2 (PET2). An exploratory analysis of PFS per investigator was conducted. <h3>Results</h3> There were 664 and 670 patients randomized to receive A+AVD and ABVD, respectively. 64%, 62%, and 58% of patients had stage IV disease, extranodal involvement at diagnosis, and B symptoms, respectively. Five-year PFS was 82.2% (95% confidence interval [CI]: 79.0–85.0) with A+AVD and 75.3% (95% CI: 71.7–78.5) with ABVD. Overall, PFS favored A+AVD (hazard ratio [HR]: 0.681; 95% CI: 0.534–0.867; P=0.002). PFS benefits were observed regardless of PET2 status and International Prognostic Score. Estimated 5-year PFS with A+AVD <i>versus</i> ABVD was 84.9% <i>versus</i> 78.9% in PET2-negative patients (HR: 0.663; 95% CI: 0.502–0.876; P=0.004), and 60.6% <i>versus</i> 45.9% in PET2-positive patients (HR: 0.702; 95% CI: 0.393–1.255; P=0.229). Treatment-emergent peripheral neuropathy (PN) resolved or improved in 85% (n=375/443) and 86% (n=245/286) of the patients with PN on A+AVD and ABVD, respectively. Secondary malignancies occurred in 19 and 29 patients with A+AVD and ABVD, respectively. A total of 131 female patients or partners of male patients reported a pregnancy; both arms showed similar proportions of ongoing pregnancies or live births. <h3>Conclusions</h3> At 5 years, A+AVD still demonstrates clinically meaningful improvement in PFS versus ABVD, independent of PET2 status, with a manageable safety profile, including resolution or improvement of PN. The PFS benefit observed with A+AVD at this important milestone suggests that A+AVD is an attractive treatment option for all patients with previously untreated stage III/IV cHL. <h3>Funding</h3> Millennium Pharmaceuticals and Seagen

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

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 &lt; 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.

Brentuximab Vedotin with Chemotherapy for Patients with Previously Untreated, Stage III/IV Classical Hodgkin Lymphoma: 5-Year Update of the ECHELON-1 Study

Brentuximab Vedotin with Chemotherapy for Patients with Previously Untreated, Stage III/IV Classical Hodgkin Lymphoma: 5-Year Update of the ECHELON-1 Study

Interim PET-results for prognosis in adults with Hodgkin lymphoma: a systematic review and meta-analysis of prognostic factor studies.

Interim PET-results for prognosis in adults with Hodgkin lymphoma: a systematic review and meta-analysis of prognostic factor studies.

Interim PET-results for prognosis in adults with Hodgkin lymphoma: a systematic review and meta-analysis of prognostic factor studies

Interim PET-results for prognosis in adults with Hodgkin lymphoma: a systematic review and meta-analysis of prognostic factor studies

PET-adapted therapy after three cycles of ABVD for all stages of Hodgkin lymphoma: results of the GATLA LH-05 trial.

The role of Ann Arbor staging in determining treatment intensity after achieving a negative positron emission tomography (PET) has not been established in classical Hodgkin lymphoma (cHL). Patients with stage I-IV cHL, received three cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and an interim PET scan (PET3). PET3-negative patients received no further therapy. PET3-positive patients received three additional cycles of ABVD plus involved-field radiation therapy or salvage chemotherapy, if refractory to ABVD, and were re-evaluated by PET scan (PET6). Study endpoints were 3-year progression-free survival (PFS) and overall survival (OS) rates. Two hundred and thirty-nine patients with early-stage and 138 with advanced-stage were evaluable. Overall, 260 patients (70%) were PET3-negative and had higher 3-year PFS (90% vs. 65%; P<0·0001) and OS (98% vs. 92%; P=0·007) rates than PET3-positive patients. All PET3-negative patients, regardless of disease stage at diagnosis, achieved similarly good PFS (90-91%; P=0·76) and OS (97-99%). The only independent prognostic factor for PFS was PET3-negativity (Hazard ratio 3·8; 95% confidence interval 2·4-6·3; P<0·0001). This study suggests that cHL patients who achieve a negative PET3 following ABVD have an excellent outcome, regardless of stage at diagnosis. An appropriately powered, phase III trial will be necessary to confirm these findings.

Risk-adapted therapy for advanced-stage Hodgkin lymphoma.

More than 80% of patients with advanced-stage Hodgkin lymphoma are now cured with contemporary treatment approaches. The ongoing challenge is how to further improve outcomes by identifying both high-risk patients who may benefit from more intensive frontline therapy to reduce the risk of relapse as well as lower-risk patients who may do just as well with less intensive therapy. Numerous trials have used an interim positron emission tomography (PET) response-adapted approach to evaluate early escalation or deescalation of therapy for patients with a positive or negative interim PET scan, respectively. Recent trials have incorporated novel agents, including brentuximab vedotin (BV) and the immune checkpoint inhibitors, in the frontline setting. Based on results of the ECHELON-1 trial, the Food and Drug Administration approved BV in combination with adriamycin, vinblastine, and dacarbazine chemotherapy for stage III to IV Hodgkin lymphoma. Improved methods to assess higher risk at diagnosis using quantitative PET metrics, such as metabolic tumor volume and total lesion glycolysis, and incorporation of emerging biomarkers may further refine patient selection for more intensive upfront therapy. The ultimate goal is to achieve the highest level of efficacy for an individual patient while minimizing the short- and long-term toxicities.

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

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. DisclosuresNo relevant conflicts of interest to declare.

The Association Between Liver and Tumor [18F]FDG Uptake in Patients with Diffuse Large B Cell Lymphoma During Chemotherapy.

The aim of this study was to explore the association between liver, mediastinum and tumor 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) uptake during chemotherapy in diffuse large B cell lymphoma (DLBCL). Nineteen patients with proven DLBCL underwent positron emission tomography (PET)/X-ray computed tomography scan at baseline, 1week and 2cycles after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy, and again after chemotherapy completion. The mean and maximal standardized uptake value (SUVmean and SUVmax) of the liver and mediastinum were measured and correlated with the tumor SUVmax, SUVsum, whole-body metabolic tumor volume (MTVwb), and total lesion glycolysis (TLG). At baseline, both the liver and mediastinum SUVmean and SUVmax correlated inversely with the tumor MTVwb or TLG (p<0.01 or 0.001). The liver SUVmean and SUVmax increased significantly after 1week of R-CHOP therapy and remained at the high level until chemotherapy completion. The mediastinum SUVmean and SUVmax remained stable during chemotherapy. The tumor SUVmax, SUVsum, MTVwb, and TLG decreased significantly after 1week of R-CHOP therapy. The change of the liver SUVmean correlated inversely with the change of tumor MTVwb and TLG after 1week of chemotherapy (p<0.05, respectively). The intersubject variability of liver and mediastinum [18F]FDG uptake ranged from 11 to 26%. The liver [18F]FDG uptake increased significantly after R-CHOP therapy. One of the possible reasons is the distribution of a greater fraction of the tracer to healthy tissues rather than tumor after effective chemotherapy. The variability of the liver [18F]FDG uptake during chemotherapy might affect the visual analysis of the interim PET scan and this needs to be confirmed in future studies with a large patient cohort. In addition, the intersubject variability of the liver and mediastinum [18F]FDG uptake should be considered.

Prognostic Value of Interim Positron Emission Tomography Among Children with Advanced Hodgkin Lymphoma in Developing Countries: Children Cancer Hospital Egypt Experience

Rationale and aim of the study: This is a retrospective, single center study was done to assess the prognostic role of 'interim' positron emission tomography (PET) performed during treatment of advanced stages HL with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) in pediatric patients.Patients and methods: Three hundred and eighty one patients with newly diagnosed Hodgkin lymphoma were enrolled. One hundred sixty five patients with early unfavorable and 216 with advanced-stage disease were treated with ABVD ± involved-field radiotherapy (IFR). PET scan was performed at baseline and after two cycles of chemotherapy. Treatment was not changed according to the results of the interim scan. PET scans reports was used using the Deauville five-point scale, blinded to treatment outcome.Results:Eighty-seven scans out of 336 were scored as positive (17.3%) and 249 (82.7%) as negative. The 5- years overall survival (OS) was 94% (95% Confidence Interval (CI) :91.5 Ð 96.6) for the whole study population, 86.2% (95% CI :78.3 - 94) for patients with interim positive scans and 97% (95% CI:94.2 - 99.3) for patients with interim negative scans (P<0.0001) [Figure:1].The 5-year Event-free survival (EFS) rate was 80% (95% CI :74.3 Ð 84.4) for the whole study population, 63.2% (95% CI :48.6 Ð 77.4) for patients with interim positive scans and 82.6% (95% CI :76.3 Ð 88.8) for patients with interim negative scans (P<0.0001) [Figure:2].In 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. These results confirm that ABVD with or without IFR is an adequate treatment for more than 70% of pediatrics patients in advanced stages HL. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Management of Early-stage Hodgkin Lymphoma: A Practice Guideline

In the past, treatment for patients with early-stage Hodgkin lymphoma consisted mainly of radiotherapy. Now, chemotherapy alone and chemoradiotherapy are treatment options. These guidelines aim to provide recommendations on the optimal management of early-stage Hodgkin lymphoma. We conducted a systematic review searching MEDLINE, EMBASE, the Cochrane Library and other literature sources from 2003 to 2015, and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Two authors independently reviewed and selected studies, and appraised the evidence quality. The document underwent internal and external review by content, methodology experts, a patient representative and clinicians in Ontario. We have issued recommendations for patients with classical Hodgkin lymphoma and with nodular lymphocyte predominant Hodgkin lymphoma; with favourable and unfavourable prognosis; and for the use of positron emission tomography to direct treatment. We have provided our interpretation of the evidence and considerations for implementation. Examples of recommendations are: ‘Patients with early-stage classical Hodgkin lymphoma should not be treated with radiotherapy alone’; ‘chemotherapy plus radiotherapy or chemotherapy alone are recommended treatment options for patients with early-stage non-bulky Hodgkin lymphoma’; ‘The Working Group does not recommend the use of a negative interim positron emission tomography scan alone to identify patients with early-stage Hodgkin lymphoma for whom radiotherapy can be omitted without a reduction in progression-free survival’. Through the use of GRADE, recommendations were geared towards patient important outcomes and their strength reflected the available evidence and its interpretation from the patients’ point of view.

Brentuximab vedotin and AVD followed by involved-site radiotherapy in early stage, unfavorable risk Hodgkin lymphoma

AbstractThis multicenter pilot study assessed the safety and efficacy of brentuximab vedotin (BV) and AVD (adriamycin, vinblastine, and dacarbazine) followed by 30 Gy involved site radiation therapy (ISRT). Patients with newly diagnosed, early stage classical Hodgkin lymphoma (HL) with unfavorable-risk features were treated with 4 cycles of BV and AVD. Patients who achieved a negative positron emission tomography (PET) scan (Deauville score of 1-3) received 30 Gy ISRT. Thirty patients received treatment and were assessable for toxicity. Twenty-nine patients completed 4 cycles of BV + AVD, and 25 patients BV + AVD + 30 Gy ISRT. No clinically significant noninfectious pneumonitis was observed. Serious adverse events (≥grade 3) were reported in 4 patients, including febrile neutropenia, peripheral neuropathy, and hypertension. After 2 and 4 cycles of BV + AVD, 90% (26 of 29) and 93% (27 or 29) of patients achieved a negative PET scan, respectively. Two patients with biopsy-proven primary refractory HL were treated off-study. All 25 patients who completed BV + AVD + ISRT achieved a complete response. With a median follow-up of 18.8 months, by intent to treat, the 1-year progression-free survival is 93.3% (95% confidence interval, 84-102). Overall, the treatment was well-tolerated with no evidence of significant pulmonary toxicity. The majority of patients (≥90%) achieved negative interim PET scans after 2 and 4 cycles of BV + AVD. Excluding the 2 primary refractory patients, all patients are disease free, suggesting that this is a highly active treatment program even in patients with substantial disease bulk. This trial was registered at www.clinicaltrials.gov as #NCT01868451.

Very low utility of surveillance imaging in early-stage classic Hodgkin lymphoma treated with a combination of doxorubicin, bleomycin, vinblastine, and dacarbazine and radiation therapy.

This study evaluated the need for surveillance imaging in early-stage classic Hodgkin lymphoma (cHL) after planned combined-modality therapy (CMT). Primary early-stage cHL patients who underwent CMT were included. Positron emission tomography (PET)/computed tomography (CT), CT, or both were performed at the initial staging, during or after chemotherapy, and for at least 2 years during follow-up. Imaging studies and medical records were reviewed to determine if and when relapse had occurred. Radiation doses and costs were also calculated from follow-up imaging. The study included 78 patients with a median follow-up of 46 months; 85% of the patients had stage II disease (32% with bulky disease). Four of 77 interim PET scans were positive; none of these patients relapsed during follow-up, which ranged from 24 to 80 months. After a total of 466 follow-up imaging studies (91% with CT and 9% with PET/CT), no cHL relapse was detected. Eleven abnormal findings were noted on surveillance imaging: 9 were false-positives, and 2 were second primary malignancies. The average cumulative dose per patient from follow-up imaging was 107 mSv, which translated into an estimated lifetime excess cancer risk of 0.5%; the estimated total costs were $296,817 according to Medicare reimbursements. Surveillance imaging with either CT or PET/CT can be omitted safely for early-stage cHL treated with a combination of doxorubicin, bleomycin, vinblastine, and dacarbazine and radiation therapy because the risk of relapse is extremely low. This observation also applies to patients with bulky disease. The elimination of surveillance imaging will also reduce healthcare expenses and cumulative radiation doses in these predominantly young patients.

Combined Use of Interim Positron Emission Tomography Scans and Serum Soluble Interleukin-2 Receptor Values Predicts Survival in Patients with Diffuse Large B-Cell Lymphoma

<Background> The prognostic impact of interim positron emission tomography scans (I-PET) for patients with diffuse large B-cell lymphoma (DLBCL) is a matter of debate because its positive predictive value (20–80%) is low. Here, we aimed to improve the prognostic impact of I-PET by combining it with interim analysis of serum soluble interleukin-2 receptor (sIL2R) levels, the levels of which at the time of diagnosis are associated with the prognosis of DLBCL.<Patients and Methods> We retrospectively examined data from DLBCL patients diagnosed at our institution between January 2006 and October 2013. Patients were included in the analysis if they met all of the following criteria: six or more cycles of rituximab plus CHOP regimen (R-CHOP); I-PET performed after 2-4 cycles of chemotherapy; and sIL2R levels measured after each cycle. Patients with primary central nervous system lymphoma, primary mediastinal large B-cell lymphoma, or transformed DLBCL from indolent lymphoma were excluded. I-PET was assessed visually according to the International Harmonization Project criteria. The interim sIL2R (I-IL2) level was defined as the value measured just before the fourth R-CHOP cycle. I-IL2 levels > 800 U/ml, or 2000 U/ml if serum creatinine was > 2.0 mg/dl (sIL2R is influenced by renal function), were regarded as positive. The primary endpoint of the study was progression-free survival (PFS). The unadjusted probabilities of PFS were estimated using the Kaplan-Meier method. The log-lank test and multivariate Cox regression analysis were used to assess the prognostic values of each clinical variable.<Results> In total, 135 patients were enrolled. The median age was 66 years (range, 34–89) and 66 patients (48.9%) were male, 27 (20%) had an ECOG performance status >1, 18 (13.3%) had bulky disease, 81 (60%) had advanced disease, and 61 (45.2%) had a high or high-intermediate International Prognostic Index (IPI) score. The median follow-up time was 25.6 months (range, 6.3–88.7) and the 2 year progression-free survival rate (2-y PFS) of the entire cohort was 72.9% (95% confidence interval (CI), 63.8–80). I-PET and I-IL2 were positive in 47 (34.8%) and 15 (11.1%) patients, respectively. Univariate analysis revealed that a high IPI score, a positive I-PET, and a positive I-IL2 had statistically significant poor prognostic effects on PFS, although gender and bulky disease did not. The three significant variables were entered into multivariate analysis, which identified positive I-PET and I-IL2 values (but not IPI) as independently associated with a poor prognosis. The 2-y PFS was 81.8% (95% CI, 70.4–89.1) for I-PET-negative and 56.3% (95% CI, 40.7–69.3; p<0.001, log rank test) for I-PET positive, respectively. Although a negative I-PET was highly predictive of a favorable outcome, a positive I-PET was of limited clinical value. The 2-y PFS for the 13 patients (9.6%) that were both I-PET- and I-IL2-positive was significantly lower than that of the remaining patients (27.7% [95% CI, 7.1–53.6] and 77.7% [95% CI, 68.4–84.6], respectively; p<0.001). Patients that were positive for both I-PET and I-IL2, rather than patients that were positive for I-PET alone, had a poor outcome.<Conclusion> DLBCL patients that were both I-PET- and I-IL2-positive suffered a high rate of progression; therefore, such patients should be targeted by novel therapeutic approaches. Because the study was based on a retrospective analysis and a limited follow-up period, further studies are needed to confirm the prognostic impact of the combined use of I-PET and I-IL2. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The predictive role of interim positron emission tomography for Hodgkin lymphoma treatment outcome is confirmed using the interpretation criteria of the Deauville five-point scale.

A retrospective, international, multicenter study was undertaken to assess: (i) the prognostic role of 'interim' positron emission tomography performed during treatment with doxorubicin, bleomycin, vinblastine and dacarbazine in patients with Hodgkin lymphoma; and (ii) the reproducibility of the Deauville five-point scale for the interpretation of interim positron emission tomography scan. Two hundred and sixty patients with newly diagnosed Hodgkin lymphoma were enrolled. Fifty-three patients with early unfavorable and 207 with advanced-stage disease were treated with doxorubicin, bleomycin, vinblastine and dacarbazine ± involved-field or consolidation radiotherapy. Positron emission tomography scan was performed at baseline and after two cycles of chemotherapy. Treatment was not changed according to the results of the interim scan. An international panel of six expert reviewers independently reported the scans using the Deauville five-point scale, blinded to treatment outcome. Forty-five scans were scored as positive (17.3%) and 215 (82.7%) as negative. After a median follow up of 37.0 (2-110) months, 252 patients are alive and eight have died. The 3-year progression-free survival rate was 83% for the whole study population, 28% for patients with interim positive scans and 95% for patients with interim negative scans (P<0.0001). The sensitivity, specificity, and negative and positive predictive values of interim positron emission tomography scans for predicting treatment outcome were 0.73, 0.94, 0.94 and 0.73, respectively. Binary concordance amongst reviewers was good (Cohen's kappa 0.69-0.84). In conclusion, the prognostic role and validity of the Deauville five-point scale for interpretation of interim positron emission tomography scans have been confirmed by the present study.

The prognostic value of interim positron emission tomography scan in patients with classical Hodgkin lymphoma

The prognostic value of interim positron emission tomography (PET) was evaluated after 2 cycles of doxorubicin, bleomycin, vinblastin and dacarbazine in classical Hodgkin lymphoma patients (n=229), based on Deauville criteria. In early stage non-bulky disease, bulky stage II disease, advanced stage low International Prognostic Score (IPS ≤2) and advanced stage (IPS ≥3), 3-year progression-free survival rates in PET2-negative vs. PET2-positive groups were 95·9% vs. 76·9% (P<0·0018), 83·3% vs. 20·0% (P=0·017), 77·0% vs. 30·0% (P<0·001) and 71·0% vs. 44·4%(P=0·155), respectively. The outcome after positive PET2 was better than previously reported. The results from non-randomized studies of PET2-guided therapy would be valuable with careful interpretation.

Interim Positron Emission Tomography Scan Predicts Early Outcomes Of Patients With Peripheral T-Cell Lymphoma

IntroductionInterim positron emission tomography (PET) scan has shown to be useful for evaluating response in Hodgkin lymphoma. And, there has been increasing interests in using interim PET for predicting outcomes in diffuse large B-cell lymphoma. However, few data are available regarding prognostic value of interim PET in patients with peripheral T cell lymphoma (PTCL). Recently, in an attempt to standardize reporting criteria for interim PET, Deauville five-point scale (5-PS), which visually assess the uptake of lesions in comparison with background mediastinal and liver uptakes, were proposed, but this was not investigated in PTCL. Therefore, the aim of this study was to determine the prognostic role of interim PET, assessed by Deauville 5-PS, in patients with PTCL treated with systemic chemotherapy. Patients and MethodsWe consecutively enrolled newly diagnosed PTCL patients, treated with systemic chemotherapy (CHOP/CHOP-like or non-anthracycline-based) and had the baseline PET data with ³1 evaluable hypermetabolic lesion between 2006 and 2012 in two Korean institutions. Patients treated with upfront chemoradiotherapy before interim PET scan were excluded. Interim PET scan was performed after 3 cycles of chemotherapy, before 1 week of the next cycle. Interim PET response was visually assessed by 5-PS and four point or higher was regarded as positive. All PET assessment was performed by 2 nuclear medicine specialists at each institution, and the discrepancy of assessment was resolved by the agreement through discussion. ResultsA total of 35 patients was included in this analysis. The median age was 60 years (range, 31-79) and 26 (74%) were male. Histologic subtypes included were PTCL, not otherwise specified in 10 (29%), extranodal NK/T cell lymphoma in 8 (23%), angioimmunoblastic T cell lymphoma in 7 (20%), anaplastic large cell lymphoma, ALK negative in 4 (11%), and others in 6 (18%). 22 patients (63%) were presented as advanced stage disease and 9 (26%) had B symptoms. ECOG performance status was ≥ 2 in 7 (20%), serum LDH level was elevated in 16 (46%), and bone marrow was involved in 5 (14%). Thus, 14 patients (40%) were classified as high risk (≥ 2 factors) by the prognostic index for PTCL (PIT). 31 patients (89%) completed planned systemic chemotherapy ± involved-field radiotherapy and 25 (71%) achieved complete response by systemic chemotherapy. 10 patients (29%) underwent consolidative autologous stem cell transplantation (ASCT).Using 5-PS, interim PET scan was visually scored as follows; 1 point in 10 patients (29%), 2 in 6 (17%), 3 in 8 (23%), 4 in 7 (20%), and 5 in 4 (11%). Among these, 11 patients (31%) had 4 point or above were considered positive for interim PET scan. With a median follow-up of 43.4 (range, 4.3-89.8) months, progression-free survival (PFS; median, 5.2 vs 38.0 months, respectively; P=0.001) and overall survival (median, 12.6 months vs not reached, respectively; P=0.004) was significantly worse in patients with positive interim PET than those with negative results. In multivariate analysis for PFS, high risk of PIT (HR, 3.67; 95% CI, 1.13-11.99) and positive interim PET (HR, 4.02; 95% CI, 1.32-12.23) were independently associated with faster disease progression, whereas consolidation with ASCT was independent prognostic factor for better PFS (HR, 0.23; 95% CI, 0.06-0.84). ConclusionVisual assessment of interim PET scan using Deauville 5-PS appears to predict early outcomes of patients with PTCL. Patients with positive interim PET shows highly predictive of extremely poor outcomes. Therefore, our findings suggest further studies regarding early stratification based on interim PET results as a response-adapted treatment strategies in patients with PTCL are needed to improve outcomes. Disclosures:No relevant conflicts of interest to declare.