Early-stage Classical Hodgkin Lymphoma Research Articles

How to treat localized Hodgkin lymphoma?

We aim to summarize the current knowledge on the management of early-stage classical Hodgkin lymphoma, with a focus on conventional strategies, incorporation of immunotherapies and exploration of novel prognostic markers. Long-term data on combined modalities (associating chemotherapy and radiotherapy) still supports their benefit in terms of progression free survival compared to chemotherapy alone in both early favourable and early unfavourable interim PET-negative classical Hodgkin Lymphoma. Novel agents, such as Brentuximab Vedotin and checkpoints inhibitors show promising and impressive results when added to first-line treatment. Various strategies have been used, mainly in phase 2 non randomized clinical trials. Interim PET-scan has limited prognostic value and its role in regimens incorporating immunotherapies is yet unknown. Other prognosis markers emerge, such as metabolic tumour volume and circulating tumour DNA. By reflecting tumour burden pretreatment and minimal residual disease on treatment, they might be useful tools guiding treatment decisions. Novel immunotherapy agents are likely to change the landscape in front-line management of classical early-stage Hodgkin lymphoma by combined modality treatment. Despite encouraging recent data, proof of their efficacy and safety on the longer term are still needed. Treatment decisions might be guided by new promising prognosis markers but their use in clinical practice is still to be determined.

Tislelizumab monotherapy in patients with previously untreated early-stage classical Hodgkin lymphoma: a real-world study.

The anti-PD-1 antibodies have been reported to show a striking effect in relapsed and refractory(R/R) classical Hodgkin lymphoma (cHL), however, there is still limited real-world data assessing the role of anti-PD-1 antibody monotherapy in early-stage cHL. In this retrospective analysis, we reported the effectiveness and safety of tislelizumab monotherapy in the first-line therapy of early-stage cHL. Twenty-three consecutive patients (10 males and 13 females) with previously untreated stage I A-II B cHL were included. At interim evaluation after 2 doses of tislelizumab monotherapy, 11 of 23 patients (47.8%) achieved complete response (CR). At the end of tislelizumab monotherapy (EOTM), objective response was observed in 22 of 23 patients (95.7%), with CR in 16 patients (69.6%). Among six patients with PR-EOTM, two patients underwent 4 cycles of ABVD chemotherapy and one patient underwent 4 cycles of tislelizumab plus AVD. One patient who developed progressive disease (PD) after 4 doses of tislelizumab subsequently underwent 4 cycles of ABVD chemotherapy. Except for four patients with CR-EOTM, consolidative radiotherapy was given to 19 patients. All patients obtained CR at the end of all treatments. With a median follow-up time of 21.3months (range, 6.9-32.7months), the estimated 2-year PFS rate and 2-year OS rate were 95.65% and 100%, respectively. Except for grade 3 lymphocyte count decreased, no other grade 3/4 TRAE was observed. In addition, no serious AE was reported. Our preliminary data observed that tislelizumab monotherapy was safe and highly effective in previously untreated early-stage cHL.

PET Project: Introducing PD-1 and ctDNA into Frontline Therapy for Early-stage Classic Hodgkin Lymphoma

PET Project: Introducing PD-1 and ctDNA into Frontline Therapy for Early-stage Classic Hodgkin Lymphoma

Early-stage classical Hodgkin lymphoma in children and adolescents: when can radiotherapy be safely omitted?

Early-stage classical Hodgkin lymphoma in children and adolescents: when can radiotherapy be safely omitted?

Brentuximab Vedotin, Nivolumab, Doxorubicin, and Dacarbazine (AN+AD) for Early Stage Classic Hodgkin Lymphoma: Interim Efficacy and Safety Results from the Single-Arm Phase 2 Study (SGN35-027 Part C)

Introduction Brentuximab vedotin (BV) and nivolumab are well tolerated and active treatments for patients (pts) with classical Hodgkin lymphoma (cHL). These agents were previously studied in first salvage therapy (overall response rate [ORR] 85%; complete response [CR] 67%) (Advani 2021) and as first-line therapy in older adults (ORR 95%) (Yasenchak 2020). In ECHELON-1 study, BV plus doxorubicin, vinblastine, and dacarbazine (A+AVD) improved overall survival (OS) by 4.5 percentage points over doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) (6-year OS estimate of 93.9% vs 89.4%) in pts with previously untreated stage III or IV cHL (Ansell 2022). In pts with limited stage I or II cHL, BV plus doxorubicin and dacarbazine (AD) treatment resulted in a CR rate of 97% at end of treatment (EOT), a promising 4-year progression-free survival (PFS) estimate of 88%, and no cases of ≥ Grade 3 peripheral neuropathy (Abramson 2021). In Part B of SGN35-027, treatment with BV, nivolumab, doxorubicin, and dacarbazine (AN+AD) showed promising preliminary activity in pts with bulky stage II or stage III/IV cHL (at EOT: ORR 93%; CR 88%) with no cases of febrile neutropenia or Grade 5 adverse events (AEs) (Lee 2021). Herein, we present interim efficacy and safety results from pts with non-bulky stage I and II cHL treated in Part C of SGN35-027. Methods SGN35-027 (NCT03646123) is an open-label, multiple part, multicenter, phase 2 clinical trial. In Part C, enrolled pts had Ann Arbor stage I or II cHL without bulky disease. Pts were treated with 4 cycles of AN+AD (BV 1.2 mg/kg [A], nivolumab 240 mg [N], doxorubicin 25 mg/m2 [A], and dacarbazine 375 mg/m2 [D]). All study drugs were each administered intravenously on Days 1 and 15 of each 28-day cycle. The primary efficacy endpoint was CR rate at EOT. Key secondary endpoints included safety and tolerability, ORR, duration of objective response (DOR), duration of complete response (DOCR), and PFS. Disease response and progression were assessed by investigator using Lugano Classification Revised Staging System for malignant lymphoma (Cheson 2014) incorporating Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) for nodal non-Hodgkin and Hodgkin Lymphomas (Cheson 2016). Results In Part C, 129 pts were enrolled, of which 125 received at least 1 dose of study treatment. Most of the 125 pts treated were White (85%) and <65 years old (91%), while approximately half were female (55%). The median age was 33.0 years (range: 18, 77 years). Pts had stage I (11%) or II (89%) cHL, without bulky disease. Of the 125 pts treated, 76 had completed EOT response assessment or discontinued treatment/study without EOT assessment (Efficacy Evaluable [EE] population) as of the data cutoff date (16-Mar-2022). Of the 76 pts in the EE population, the overall CR rate was 91% (95% CI: 81.9, 96.2) at EOT. The ORR was 93% (95% CI: 85.3, 97.8), with 69 pts achieving CR and 2 pts achieving partial response (PR) at EOT. Of the 125 pts treated, no pts discontinued treatment (all study drugs) early due to treatment-emergent AEs (TEAEs) and 53% of pts had any dose modifications including any dose delay (25%), reduction (8%), and elimination (29%) due to AEs. As of 16-Mar-2022, 35% of pts experienced ≥ Grade 3 TEAEs. Nausea, peripheral sensory neuropathy, and fatigue were the most frequently reported treatment-related TEAEs (66%, 42%, and 38% of pts, respectively). Notably, only 2 pts (2%) experienced ≥ Grade 3 peripheral sensory neuropathy, of which were considered treatment-related. No TEAEs led to death, and no cases of febrile neutropenia were reported. Ten pts (8%) experienced treatment-related serious TEAEs; most commonly pyrexia (2%) and pneumonitis (2%). Twenty-one pts (17%) experienced treatment-emergent immune-mediated AEs; most commonly hyperthyroidism (6%), hypothyroidism (6%), maculo-papular rash (3%), and pneumonitis (2%). Conclusions Interim efficacy and safety results indicate that AN+AD has promising efficacy and is well tolerated by pts with early stage cHL. No new safety signals were observed, and no pts had discontinued the treatment regimen early due to AEs. Omitting bleomycin and vinblastine may have contributed to absence of certain AEs, such as febrile neutropenia. Part C of this study is ongoing and updated efficacy and safety results will be presented.

Behandlung früher und intermediärer Stadien des Hodgkin-Lymphoms

BackgroundIn early stage classical Hodgkin lymphoma (cHL), reduction of treatment-associated toxicity while maintaining achieved high cure rate remains a major goal.ObjectivesEvidence-based development of current treatment recommendations for early stage favorable and unfavorable HL.MethodsEvaluation of current randomized trials, meta-analyses, and relevant retrospective analyses with regard to tumor control, overall survival, and safety data.Results and conclusionsTwo cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and 20 Gy involved-site radiotherapy (IS-RT) are still regarded as standard in early stage favorable HL and are also used in the older patients, unless there are contraindications. Compared to standard treatment, the 18Ffluorodeoxyglucose (FDG) positron emission tomography (PET)-based RT-approach resulted in significantly lower tumor control in the RAPID, H10, and HD16 trials and can therefore only be considered as an individual approach after weighing the benefits and risks of long-term toxicity of RT. In early stage unfavorable HL, two cycles of escalated(e)BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) followed by two cycles of ABVD (“2 + 2”) result in significantly higher progression-free survival (PFS) compared to four cycles of ABVD. The HD17 trial showed that “2 + 2” additionally enables a PET-guided RT-approach without impairment of tumor control, i.e., omission of RT in those patients with negative PET after “2 + 2”. Therefore, “2 + 2” + PET-guided RT is recommended as the new standard in patients ≤ 60 years of age. In patients older than 60 years, combined modality treatment (CMT) with two cycles of ABVD followed by two cycles of AVD and 30 Gy IS-RT is still recommended.

Patterns of care and outcomes of early stage I–II Hodgkin lymphoma treated with or without radiation therapy

Omission of radiotherapy in the upfront management of early-stage classic Hodgkin lymphoma (cHL) has become more common with time. We report patterns of care and outcomes of stage I–II cHL treated with chemotherapy (CT) only versus CT and radiotherapy (combined modality therapy, CMT). From the National Cancer Database, we identified 28,327 early-stage cHL patients treated with CT (n = 15,798) or CMT (n = 12,529) from 2004 to 2018. CMT utilization declined over the period from 58% to 34%. With median follow-up of 6.2 years, the 5- and 10-year overall survival for CT versus CMT was 93.3% versus 96.9% (p < 0.001) and 88.7% versus 93.5% (p < 0.001), respectively. On multivariable analysis, uninsured (OR 0.75, p < 0.001) and Black patients (OR 0.86, p = 0.02) were less likely to receive CMT, and treatment with CT was predictive of death (OR 2.0, p < 0.001). This report highlights real-world outcomes in early-stage cHL, with worse survival with CT and notable disparities in CMT utilization.

Combined modality therapy for early-stage Hodgkin lymphoma in the PET era: A real-world study.

e19532 Background: The traditional approach to the treatment of early-stage classical Hodgkin lymphoma (cHL) has been combined modality therapy (CMT) with both chemotherapy and radiotherapy (RT). CMT has shown improved disease control, but RT can lead to long-term adverse effects, including secondary malignancies and cardiac toxicity. Multiple clinical trials have assessed treatment de-escalation strategies to chemotherapy-alone regimens, but results are conflicting. We aimed to assess the real-world implications of these trials by comparing patient outcomes based upon treatment with CMT or chemotherapy-alone. Furthermore, we proposed to assess differences in treatment outcomes stratified by disease bulk, favorable/unfavorable disease, and PET2 response. Methods: We conducted a retrospective, multi-center cohort study of consecutive adult patients with early-stage (stage IA-IIB) cHL treated between January 2010-December 2020. Baseline characteristics, treatment modality, and outcomes were abstracted by chart review. Available PET2 scans (n=110) were independently reviewed by a blinded nuclear radiologist. Deauville score (DS) ≥4 was characterized as positive (+), and DS≤3 negative (-). All analysis was conducted using intention-to-treat principles based upon the initial treatment plan (CMT or chemotherapy-alone). Results: In 125 patients [58% male, median age 34 (range, 18-78)] with early-stage cHL, CMT was intended in 63 (50%) patients, with chemotherapy-alone in 62 (50%). Bulky disease was observed in 43 (34%), unfavorable disease in 81 (65%), and 15 (14%) were found to be PET2+. With median follow-up of 59.8 months (95%CI, 48.6 to 71.0), 5 (4%) deaths occurred, and 17 (14%) patients had relapsed/refractory disease. No significant differences in overall survival (OS) were seen based upon treatment intention. However, there was substantially reduced progression-free survival (PFS) (Table) with chemotherapy-alone in the whole cohort, and also in those with bulky, unfavorable, and PET2+ disease. No significant PFS differences were seen based upon treatment intention for patients with non-bulky, favorable, or PET2- disease. Conclusions: Based on our real-world experience, CMT appears particularly beneficial for patients with bulky disease, unfavorable prognostic factors, and PET2+ disease. However, while recent trials showed a benefit of CMT in non-bulky, favorable and PET2- patients, chemotherapy-alone may be comparable for these patients in actual clinical practice.[Table: see text]

A real-world study of combined modality therapy for early-stage Hodgkin lymphoma: too little treatment impacts outcome

AbstractMultiple clinical trials have assessed de-escalation strategies from combined modality therapy (CMT) to chemotherapy-alone for the treatment of early-stage classical Hodgkin lymphoma (cHL), confirming similar outcomes. The application of these data to the real-world is limited, however. We conducted a retrospective, multicenter cohort study comparing CMT vs chemotherapy-alone in patients with early-stage cHL (stage IA-IIB) treated between January 2010 and December 2020. Positron emission tomography (PET) scans after chemotherapy cycle 2 (PET2) were independently reviewed by a nuclear radiologist (Deauville score ≥4, positive; ≤3, negative). Patient outcomes were compared by using an intention-to-treat analysis. Among 125 patients (CMT, n = 63; chemotherapy-alone, n = 62) with a median follow-up of 59.8 months (95% CI, 48.6-71.0), no differences in overall survival were observed (5-year overall survival, CMT 98.0% vs chemotherapy-alone 95.1%; log-rank test, P = .38). However, there was reduced progression-free survival (PFS) with chemotherapy-alone among all patients (2-year PFS, CMT 95.1% vs chemotherapy-alone 75.3%; log-rank test, P = .005) and in those with bulky (n = 43; log-rank test, P < .001), unfavorable (n = 81; log-rank test, P = .002), or PET2-positive (n = 15; log-rank test, P = .02) disease. No significant differences in PFS were seen for patients with non-bulky (log-rank test, P = .35), favorable (log-rank test, P = .62), or PET2-negative (log-rank test, P = .19) disease. Based on our real-world experience, CMT seems beneficial for patients with early-stage cHL, especially those with PET2-positive and unfavorable disease. Chemotherapy-alone regimens can lead to comparable outcomes for patients with favorable, non-bulky, or PET2-negative disease. We conclude that although results seen in clinical trials are replicated in certain patient subgroups, other subgroups not fitting trial criteria do poorly when radiotherapy is excluded.

Prognostic role of red blood cell distribution width and platelet/lymphocyte ratio in early-stage classical Hodgkin lymphoma.

Background: To investigate the prognostic role of redblood cell distribution width (RDW) and platelet/lymphocyte ratio (PLR) in early-stage classical Hodgkin lymphoma (cHL). Materials & methods: Data from 402 patients with newly diagnosed early-stage cHL were retrospectively collected. The impact of factors on complete response (CR) rate and freedom from progression (FFP) was analyzed. Results: High PLR was associated with lower CR, but high RDW was not. The univariate analysis showed that RDW and PLR were predictive of FFP. On multivariate analysis, high PLR was an independent risk factor for inferior FFP. Subgroup analysis and a prognostic model for FFP based on PLR validated the prognostic role of PLR. Conclusion: PLR was a robust prognostic factor for newly diagnosed early-stage cHL.

Limited, But Not Eliminated, Excess Long-Term Morbidity in Stage I-IIA Hodgkin Lymphoma Treated With Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine and Limited-Field Radiotherapy

PURPOSEBalancing disease control and toxicity from chemotherapy and radiotherapy (RT) when treating early-stage classical Hodgkin lymphoma (cHL) is important. Available data on long-term toxicity after RT for cHL mostly refer to RT techniques no longer in use. We aimed to describe long-term toxicity from modern limited-field (LF)-RT after two or four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).PATIENTS AND METHODSThis study included all patients with cHL treated with two or four cycles of ABVD and 30 Gy LF-RT during 1999-2005 in Sweden. Patients (n = 215) and comparators (n = 860), matched for age, gender, and region of residence, were cross-checked against national health registries for malignancies, diseases of the circulatory system (DCS), and diseases of the respiratory system (DRS) from the day of diagnosis of cHL.RESULTSThe risk of a malignancy was higher for patients than comparators, hazard ratio (HR) 1.5 (95% CI, 1.0 to 2.4), as was the risk for DCS 1.5 (95% CI, 1.1 to 2.0) and for DRS 2.6 (95% CI, 1.6 to 4.3). The median follow-up was 16 years (range, 12-19 years). Of individual diagnoses in DCS, only venous thromboembolism was statistically significantly elevated. If the first 6 months (ie, time of active treatment for cHL) were excluded and censoring at relapse of cHL or diagnosis of any malignancy, the increased HR for venous thromboembolism diminished. Most of the excess risk for DRS consisted of asthma, HR 3.5 (95% CI, 1.8 to 6.8). Patients diagnosed with DRS were significantly younger than comparators.CONCLUSIONCompared with toxicity from earlier RT techniques, excess morbidity was not eliminated, but lower than previously reported. The elevated risk of DRS was driven by diagnosis of asthma, which could in part be explained by misdiagnosis of persisting pulmonary toxicity.

Consolidative Radiation with Chemotherapy in Early Stage Classical Hodgkin Lymphoma with Unfavorable Risk: The Kentucky Experience

Introduction:Early stage classical Hodgkin lymphoma (cHL) carries good prognosis. Patients with B symptoms have been found to have unfavorable risk. Due to overall good outcome, studies are focusing on minimizing toxicity by omission of consolidative radiation. The aim of our study is to review outcome of this cohort in a population based analysis.Methods:All early stage (stage I and II) cHL adult patients diagnosed 2005-2014 were collected through Kentucky Cancer Registry (KCR). Patients reported to have had B symptoms (Unexplained fevers >38°C; drenching night sweats; or weight loss >10% of body weight within 6 months prior to diagnosis) were included in the current study. Baseline characteristics as well as survival outcome were compared between chemotherapy alone and combined chemo-radiation treatment. Pearson Chi-square, log-rank, and cox regression tests were used in the analysis. To minimize selection bias, events during the first 6 months of therapy were censored. 10-year survival data were then compared to Surveillance, Epidemiology and End Results (SEER) registry.Results:A total of 130 adult patients were included in the study; 76 patients got chemotherapy alone and 54 patients got chemo-radiation therapy. Median age was 35 (ranged 18-88). Most patients were younger than 50 year-old (76.9%). Most patients had nodular sclerosis (N=91) while 29 patients had unknown histology. There was no statistical difference in pretreatment features between the group receiving chemotherapy and those who received chemo-radiation (See table).There was no difference in 10-years overall survival between the chemotherapy group (73%) and chemo-radiation (80%) (p=0.830) (See figure). When adjusting for multivariate analysis, age younger than 50 was the only statistically significant variable affecting survival with a HR 0.17 (95% CI: 0.058-0.505). Only 4 (5.3%) patients developed second primary cancer in chemotherapy alone versus 1 (1.9%) in chemo-radiation therapy (p =0.4).Compared to overall survival in SEER database, younger patients (<50 years old) had worse overall survival (81.9% vs 85.5%) (p<0.001). This was not observed in the older population.Conclusion:Our study shows lack of benefit of the combined approach for the management of unfavorable prognosis classical Hodgkin lymphoma in a population based analysis. Younger patients had worse outcome when compared to SEER registry while older age group had worse prognosis with the available therapies and might benefit from alternative interventions. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Initial treatment strategy for classical Hodgkin lymphoma in adults

Four cycles of ABVD followed by 30 Gy IFRT (ISRT) is a standard regimen, as an initial treatment, for patients with early-stage classical Hodgkin lymphoma (cHL), whereas 2 cycles of ABVD followed by 20 Gy IFRT (ISRT) is an alternative regimen for those with favorable early-stage cHL. For patients with unfavorable early-stage cHL including bulky disease, local radiotherapy can be safely omitted if negative findings on interim PET are obtained after 2 cycles of escalated BEACOPP plus 2 cycles of ABVD. ABVD (6/8 cycles) or brentuximab vedotin (BV) with concurrent AVD (6 cycles) is a standard regimen for patients with advanced-stage cHL. For elderly cHL patients (60 years of age or older) and multiple comorbidities, the risk of treatment-related adverse events is higher, which can potentially lead to poor outcomes. BV with sequential AVD therapy, which is a unique combination strategy, has been developed for elderly cHL patients. The combination of anti-PD-1 antibodies with AVD therapies is currently being evaluated in some clinical trials. This review includes current evidence that primarily focuses on randomized clinical trials for newly diagnosed adult cHL patients and management points in clinical practice for those patients.

Enhanced Outcome Prediction in Early Stage Classical Hodgkin Lymphoma Using Pre-Treatment Biomarkers and Interim PET (BioPET); A Sub-Analysis of the UK NCRI RAPID Trial

Enhanced Outcome Prediction in Early Stage Classical Hodgkin Lymphoma Using Pre-Treatment Biomarkers and Interim PET (BioPET); A Sub-Analysis of the UK NCRI RAPID Trial

Outcomes in Patients with Classic Hodgkin Lymphoma Treated with ABVD: A Single-center Retrospective Study.

Objective Classic Hodgkin lymphoma (CHL) has been regarded as a curable disease when treated appropriately, especially in younger patients, and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) has been regarded as the standard regimen. However, a relatively poor prognosis has been reported in older patients with CHL, and the efficacy and tolerability of the ABVD regimen has not been fully elucidated. We retrospectively investigated the outcomes in patients with CHL treated with ABVD at our institute. Methods Twenty-five patients were evaluated; 14 were ≤60 years of age, and 11 were >60 years of age (older group). Results The ABVD doses were reduced in all patients in the older group; the median average relative dose intensity was 0.58. In the older group, the 5-year overall survival (OS) and median OS were 100% and not reached, respectively, for patients with early-stage CHL and 66.7% and not reached, respectively, for those with advanced-stage CHL. No patients died of CHL, and only one treatment-related death was observed in the older group. Conclusion ABVD with dose attenuation may represent a feasible and effective strategy for the treatment of older patients with CHL in clinical practice, particularly in those with early-stage disease, although the optimal degree of attenuation remains unclear.

Ten-year survival outcomes for patients with early stage classical Hodgkin lymphoma: An analysis from Kentucky Cancer Registry

Objective/BackgroundEarly stage classical Hodgkin lymphoma (cHL) has an excellent outcome. Recent studies focus on decreasing toxicity related to the addition of radiation along with chemotherapy. Real-life reporting of the addition of radiation to chemotherapy is lacking. This study investigates the outcomes obtained from a statewide cancer registry for early stage cHL patients treated with chemotherapy alone (CT) versus patients treated with the combined modality of chemotherapy and radiation (CMT). MethodsA retrospective study of cHL patients diagnosed and treated was identified using a statewide cancer registry from 2005 to 2014. Patients with early stage disease (I, II) were then grouped on the basis of the presence of B symptoms into favorable and unfavorable groups. Baseline characteristics (age, gender, extranodal involvement, and histology) as well as overall survival were compared for both groups depending on whether they received CT or CMT as first line therapy for their cHL. ResultsA total of 961 patients were identified; of those, 127 were excluded as they received only radiation or another form of treatment. Of the remaining patients, 293 were categorized as early stage favorable cHL (Group 1) and 130 adults were in the unfavorable cHL (Group 2). There were 335 patients with advanced stage cHL (Group 3) and 76 patients in an unknown stage. The 10-year overall survival for Group 1 was 81.3% versus 76.3% for Group 2 and 52.7% for Group 3. For Group 1, 10-year overall survival was 86.7% with CMT versus 75.1% for those receiving CT only (p = .004). For Group 2, there was no difference in 10-year overall survival between the CMT group (80.0%) and CT (72.5%) (p = .73). ConclusionWhile radiation therapy might increase long-term toxicity in cHL, in our large data cohort, radiotherapy consolidation as part of the initial therapy for early stage disease provides superior survival at 10 years, especially in favorable risk cHL.

A PET Radiomics Model to Predict Refractory Mediastinal Hodgkin Lymphoma

First-order radiomic features, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), are associated with disease progression in early-stage classical Hodgkin lymphoma (HL). We hypothesized that a model incorporating first- and second-order radiomic features would more accurately predict outcome than MTV or TLG alone. We assessed whether radiomic features extracted from baseline PET scans predicted relapsed or refractory disease status in a cohort of 251 patients with stage I-II HL who were managed at a tertiary cancer center. Models were developed and tested using a machine-learning algorithm. Features extracted from mediastinal sites were highly predictive of primary refractory disease. A model incorporating 5 of the most predictive features had an area under the curve (AUC) of 95.2% and total error rate of 1.8%. By comparison, the AUC was 78% for both MTV and TLG and was 65% for maximum standardize uptake value (SUVmax). Furthermore, among the patients with refractory mediastinal disease, our model distinguished those who were successfully salvaged from those who ultimately died of HL. We conclude that our PET radiomic model may improve upfront stratification of early-stage HL patients with mediastinal disease and thus contribute to risk-adapted, individualized management.

297P - Chemotherapy versus combined chemoradiotherapy: Survival patterns among patients with early stage classical Hodgkin lymphoma

297P - Chemotherapy versus combined chemoradiotherapy: Survival patterns among patients with early stage classical Hodgkin lymphoma

The Impact of PET/CT Staging on the Incidence of Late Hodgkin Lymphoma Relapse for Patients Treated with Limited Radiation Fields

A recent pooled analysis1 reported a risk of late Hodgkin lymphoma relapse (LR) between 5-20 years after treatment of early stage classical Hodgkin lymphoma (HL) treated with involved field radiotherapy (IFRT). PET/CT staging was not standardly performed in the included trials, but our institution routinely performed PET/CT in this era. This study aims to assess the impact of PET/CT staging on the incidence of LR for patients with early stage HL treated in the IFSRT era. We performed a retrospective assessment of all patients treated for stage I-II HL with multiagent chemotherapy followed by involved field or involved site radiotherapy (IFSRT) from 2000 to 2011 at our institution. The German Hodgkin Study Group (GHSG) risk stratification criteria system was utilized. Patients routinely underwent bone marrow biopsy and PET/CT scan for staging. Overall (OS) and event-free survival (EFS) was estimated using the Kaplan-Meier method. Any recurrence or death was considered an event. Incidence of relapse was estimated using the cumulative incidence function. LR was defined as any relapse occurring ≥ 5 years from initial diagnosis. A total of 134 patients were included. Median age was 34 years (range, 4-77). Stage: 15% IA, 1% IB, 66% IIA, and 17% IIB. 60% were unfavorable risk. 77% had disease in the mediastinum. 109 patients (81%) completed a staging PET/CT. ABVD (93%) was the most commonly prescribed chemotherapy. Radiation dose and fractionation ranged from 20-40 Gy in 1.5-2 Gy fractions. The median follow up for all patients and those staged with PET/CT was 8.1 and 8.2 years respectively. A total of 27% have more than 10 years of follow up. OS for the entire cohort at 5, 10 and 15 years was 97.5%, 96.0%, and 88.9% respectively. EFS for the entire cohort at 5, 10, and 15 years was 96.6%, 94.8%, 85.2% respectively. Only 3 of 134 patients experienced a relapse and of these 2 have died. Two of the 3 patients who relapsed did not have a staging PET/CT. Relapses occurred at 11, 18, and 30 months after treatment, corresponding to a cumulative incidence of relapse at 3 years of 2.6%. No late relapses were observed (>5 years). Continued decline in OS and EFS beyond 5 years was due to death from unrelated causes and was limited to patients over the age of 70 years at initial HL diagnosis. 5 patients developed a non-skin secondary malignancy at a median time of 6.3 years after diagnosis. Of these malignancies, 1 was fatal (acute myeloid leukemia). Based on the findings of Brockelmann et al., the anticipated incidence of late relapse should have been between 2-5%, however in this cohort with a majority of patients undergoing staging PET/CT, there were no late relapses. Our results provide support for further study of the hypothesis that the use of PET/CT at the time of initial staging may be associated with a lower risk of late relapse. 1. Brockelmann et al. Late Relapse of Classical HL: An Analysis of the GHSG HD7 to HD12 Trials. JCO. 2017.

Limited-Stage Hodgkin Lymphoma: Minimizing Toxicity.

Early-stage classic Hodgkin lymphoma has been highly curable using extended-field radiation therapy (RT) alone, combined-modality therapy consisting of chemotherapy and RT, and more recently chemotherapy alone. Radiation therapy either to an extended field (extended-field RT) or to various iterations of an involved field (involved-field RT) is potentially associated with late morbidity and mortality, particularly second primary cancers and cardiovascular complications. Treatment with chemotherapy alone, when possible, can achieve a high cure rate while avoiding these risks. This review describes the evolution of treatment for early-stage classic Hodgkin lymphoma.