Treatment Of Hodgkin Lymphoma Research Articles

Experience in the treatment of Hodgkin’s lymphoma associated with HIV

Background. Among malignant neoplasms in HIV-infected patients lymphomas occupy a special place due to the high incidence, course characteristics, and difficulties that arise during diagnosis and during antitumor drug therapy. Hodgkin’s lymphoma (HL) is not an AIDS indicating disease, but the risk of its development in people infected with HIV is 5–25 times higher than the incidence of HL in the general population. Prior to the use of antiretroviral therapy, the results of standard chemotherapy in HIV-infected patients with HL were significantly worse than in HIV-negative patients. One of the main requirements for drug treatment of this group of patients is the simultaneous use of antiretroviral therapy and chemotherapy. The aim was to study the clinical characteristics and results of treatment of HL in the presence of HIV infection. Materials and methods. The analysis included 24 HL patients with HIV infection who received treatment in the Department of Radiation and Drug Therapy of Hemoblastoses of the MRRC in the period from 2018 to 2022. Treatment program selection was in accordance with the HL treatment protocol developed at our Center. Patients received 4–6 cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) or 6 cycles of BEACORP (bleomycin, vepesid, doxorubicin, cyclophosphamide, vincristine, dacarbazine, prednisolone) chemotherapy according to the stage of the disease and the risk factors generally accepted for patients with HL. The response to therapy was assessed according to the Lugano-2014 criteria. Descriptive statistics methods were used. Overall survival and progression-free survival were analyzed using the Kaplan-Meier method. Results. HL occurring against the background of HIV is most often represented by a widespread nodal and extranodal lesion, accompanied by symptoms of intoxication (B-symptoms). The use of standard CT regimens as induction therapy for HL in the presence of HIV makes it possible to obtain satisfactory immediate and long-term results of treatment. In our study complete and partial responses were achieved in 94.1 %. With a median follow-up of 12 months survival without progression and overall survival were 75 % and 100 % respectively.

Pilot study of lung cancer screening for survivors of Hodgkin lymphoma.

Hodgkin lymphoma (HL) treatment increases the risk of lung cancer. Most HL survivors are not eligible for lung cancer screening (LCS) programs developed for the general population, and the utility of these programs has not been tested in HL survivors. We ran a LCS pilot in HL survivors to describe screening uptake, participant characteristics, impact of a decision aid and screen findings. HL survivors treated ≥5 years ago with mustine/procarbazine and/or thoracic radiation, were identified from a follow-up database and invited to participate. Participants underwent a low-dose computed tomography (LDCT) reported using protocols validated for the general population. Two hundred and eighteen individuals were invited, 123 were eligible, 102 were screened (58% response rate): 58% female, median age 52 years, median 22 years since HL treatment; 91.4% were deemed to have made an informed decision; participation was not influenced by age, sex, years since treatment or deprivation. Only three of 35 ever-smokers met criteria for LCS through the program aimed at the general population. Baseline LDCT results were: 90 (88.2%) negative, ten (9.8%) indeterminate, two (2.0%) positive. Two 3-month surveillance scans were positive. Of four positive scans, two patients were diagnosed with small-cell lung cancer; one underwent curative surgery. Coronary artery calcification was detected in 36.3%, and clinically significant incidental findings in 2.9%. LDCT protocols validated in ever-smokers can detect asymptomatic early-stage lung cancers in HL survivors. This finding, together with screening uptake and low false positive rates, supports further research to implement LCS for HL survivors (clinicaltrials gov. Identifier: NCT04986189.).

The role of radiotherapy in patients with refractory Hodgkin's lymphoma after treatment with brentuximab vedotin and/or immune checkpoint inhibitors

BackgroundApproximately 10%–30% of patients with Hodgkin's lymphoma (HL) experience relapse or refractory (R/R) disease after first-line standard therapy. Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) have important roles in the salvage treatment of R/R HL. However, subsequent treatment for HL refractory to BV and/or ICI treatment is challenging. MethodsWe retrospectively analyzed patients in two institutions who had R/R HL, experienced BV or ICI treatment failure, and received radiotherapy (RT) thereafter. The overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were analyzed. ResultsOverall, 19 patients were enrolled. First-line systemic therapy comprised doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD, 84.2%); AVD plus ICIs (10.5%); and bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP, 5.3%). After first-line therapy, 15 (78.9%) and four patients (21.1%) had refractory disease and relapsed, respectively. After R/R HL diagnosis, six (31.6%), two (10.5%), and 11 (57.9%) patients received BV and ICIs concurrently, BV monotherapy, and ICI monotherapy, respectively. All patients received intensity-modulated RT (n = 12, 63.2%) or volumetric modulated arc therapy (VMAT; n = 7, 36.8%). The ORR as well as the complete response (CR) rate was 100%; the median DOR to RT was 17.2 months (range, 7.9–46.7 months). Two patients showed progression outside the radiation field; one patient had extensive in-field, out-of-field, nodal, and extranodal relapse. With a median follow-up time of 16.2 months (range, 9.2–23.2 months), the 1-year PFS and OS were 84.4% and 100%, respectively. PFS was associated with extranodal involvement (P = 0.019) and gross tumor volume (P = 0.044). All patients tolerated RT well without adverse events of grade ≥ 3. ConclusionRT is effective and safe for treating HL refractory to BV or ICIs and has the potential to be part of a comprehensive strategy for HL.

Relation between coronary artery calcium score and cardiovascular events in Hodgkin lymphoma survivors: a cross-sectional matched cohort study

Abstract Introduction Long-term survival after Hodgkin lymphoma (HL) has improved significantly over the past years, due to enhanced treatment options. Thoracic radiotherapy is still one of the corner stones of HL treatment, but is associated with increased risk of cardiovascular events. As HL is often diagnosed at young age, long-term follow-up including screening for coronary artery disease (CAD) is recommended. Purpose This study aims to evaluate the presence and distribution of coronary artery calcium in relation to cardiovascular events in HL patients treated with thoracic radiotherapy compared to a non-cancer control group. Methods Consecutive HL patients treated with thoracic radiotherapy, who underwent evaluation for asymptomatic CAD with coronary computed tomography angiography (CCTA) > 10 years after irradiation between 2002 and 2022 were included. HL patients were matched 1:1 to non-cancer patients on gender, age, cardiovascular risk factors and statin use. Differences in coronary artery calcium score (CACS), stenosis severity and cardiovascular events between the two groups were compared. Results The total study population consisted of 194 patients of whom 97 patients had a prior HL diagnosis and 97 patients had no history of cancer. Elevated CACS was seen in 50.5% of the HL patients (N=49) and 30.9% of the control patients (N=30). HL survivors had an odds ratio of 2.28 [95% CI: 1.22 – 4.28] for having a CACS > 0 compared to the matched non-cancer population (p=0.006). Distribution pattern of coronary calcium differed significantly with the prevalence of a CACS above the 90th percentile (17.5% in HL survivors versus 4.7% in the matched population, p=0.005). Also coronary artery stenosis was more prevalent in the HL population than in the control population (39.2% versus 15.5% respectively, p=<0.001). Nine HL patients experienced an event during the follow-up period including two patients with a CACS of zero. No events were observed in the control population. Conclusion This study shows that in a matched study population, HL survivors have a higher prevalence of a CACS > 0 and an increased risk of cardiovascular events after thoracic irradiation compared to a matched non-cancer control group.Distribution of CACS percentiles

The role of FDG-PET scanning and PET-adapted therapy in the primary treatment of Hodgkin lymphoma: A primer for clinicians

The evolving treatment paradigm for classical Hodgkin lymphoma (cHL) remains focused on maintaining high rates of progression-free survival (PFS) and overall survival (OS), while seeking to reduce both short-term and late toxicities from chemotherapy and radiation. Functional imaging with fluoro-deoxyglucose (FDG)‑positron emission tomography (PET) combined with computed tomography (CT) is recognized as standard for staging and response evaluation of Hodgkin lymphoma (HL). Recent randomized controlled trials evaluating FDG-PET-guided therapy for patients with limited stage and advanced stage Hodgkin lymphoma provide clinicians and patients with meaningful data upon which to base individualized treatment approaches. FDG‑PET scanning after two cycles of therapy (interim PET or PET2) represents the most important determinant of further appropriate treatment and subsequent outcomes, and is now the cornerstone of risk-adapted therapy for all patients receiving curative-intent initial therapy for Hodgkin lymphoma. For patients with limited stage cHL, post-chemotherapy assessment (after two or four cycles of treatment depending on the regimen used) is also a key determinant of the need for the addition of involved site or nodal radiation as part of combined modality therapy. This review summarizes the important role of interim and end of chemotherapy FDG-PET scanning to guide individualized initial therapy for patients to achieve optimal treatment outcomes.

Safety and Efficacy of Immune Checkpoint Inhibitors in the Treatment of Hodgkin Lymphoma in People Living with Human Immunodeficiency Virus: A Case Series

Introduction: Immune checkpoint inhibitors (ICI) have changed the landscape of cancer treatment. They work by disrupting the binding of immune checkpoint proteins, such as PD-1, PD-L1, and CTLA-4, which function to prevent over-activation of the immune system. By interrupting this binding, the body's natural immune response against cancer cells is enhanced. Nivolumab and pembrolizumab, two ICIs that target PD-1, are approved for use in relapsed/refractory Hodgkin lymphoma (HL). HIV is associated with higher rates of cancer, including HL. Several studies have demonstrated the safety of ICI in people with HIV (PWH) in many types of cancer. Unfortunately, many cancer clinical trials continue to exclude PWH without consideration of long-term adherence to highly active antiretroviral therapy (HAART), normal CD4+ counts, or undetectable viral loads because of fear regarding increased adverse events (AEs) and poor outcomes. In addition, studies have shown that PWH diagnosed with cancer are less likely to receive any cancer treatment. Here, we present three cases of PWH diagnosed with HL and treated with an ICI and examine their outcomes and ICI-related AEs. In addition, we discuss five matched cases of people without HIV infection diagnosed with HL and treated with an ICI. Methods: A retrospective study was performed for HL patients at an NCI-designated comprehensive cancer center from 2015 to 2022, diagnosed with HIV (confirmed with antibody testing) and treated with an ICI. Three patients met these criteria. HIV-negative matches for the above patients were identified based on diagnosis, treatment, stage, sex, and age. Five patients with HL without HIV infection were identified as appropriate matches based on these criteria. Demographic data and clinical outcomes data were collected from the electronic medical record. The common terminology criteria for adverse events (CTCAE) were used to classify and grade AEs. Due to a small sample size, statistical analyses and comparisons were not performed between PWH and PWOH Results: Demographic data (Table 1) and clinical response/outcome data (Table 2) are shown for all patients. Patients 1, 2, and 3 were HIV positive, while patients 4, 5, 6, 7, and 8 were HIV negative. ICI-related AEs were documented in three patients, one with and two without HIV. Patient 1, who was not compliant with HAART (CD4+ 70, viral load 1.39x10 6), experienced grade 4 myocarditis (confirmed on cardiac MRI) after cycle 2 with nivolumab, with pulseless electrical activity requiring pressor support and mechanical ventilation for four days, along with high-dose steroid taper, IV diuresis, and initiation of guideline-directed medical therapy (GDMT). Nivolumab was discontinued, and the patient was lost to follow-up with reported death three months later, attributed to HL. Patient 7 developed symptomatic grade 2 hypothyroidism on nivolumab after two cycles, requiring levothyroxine, to which the patient responded appropriately. Nivolumab was continued. Patient 8 experienced grade 3 myocarditis (confirmed on cardiac MRI) after cycle 7 of pembrolizumab, with hospitalization for IV diuretics and GDMT initiation. Pembrolizumab was discontinued. Discussion: In conclusion, ICIs are a therapeutic option for the treatment of HL in PWH. This limited case series suggests that PWH on long-term HAART tolerate ICIs well. The patient in our study who was not compliant with HAART experienced grade 4 myocarditis, with death attributed to lymphoma three months later. This may suggest an increased risk of ICI-related AEs and poorer outcomes in patients not on HAART and/or with poorly controlled HIV. However, further studies are required to investigate this risk, as our sample size was too small to draw statistically meaningful conclusions. Interestingly, one patient without HIV infection also experienced ICI-related myocarditis, but of less severe grade (grade 3 versus grade 4) than the patient with HIV. Most patients from both groups had an overall survival (OS) of more than two years, which may suggest that ICIs are not associated with decreased OS in patients with HIV infection. Unfortunately, our study was limited by the sample size, and statistical comparison of patients with and without HIV infection could not be performed. Further research is needed to investigate the tolerance and efficacy of ICIs as therapeutic options in PWH with Hodgkin lymphoma.

Hypertension and Related-Disorders in Hodgkin Lymphoma Patients Identified from Epic Cosmos System

Recent advancements in Hodgkin lymphoma (HL) treatment have significantly improved disease-free survival rates. However, survivors face a higher burden of long-term comorbidities and non-oncologic mortality compared to their peers. Studying survivorship has been challenging due to the time required for comorbidities to develop, patient loss to follow-up, variable disease-specific treatments, and variations across age groups of survivors. In this context, the Cosmos system offers a validated population-based informatics approach to establishing observational relationships between therapy and longitudinal non-oncologic outcomes, with the potential to enhance clinical care. Cosmos, a data science tool based on the Epic Electronic Medical Record (EMR) system, utilizes a HIPAA-defined limited centralized data set from various US health care systems. At the time of this submission, the data set encompasses 152,450,619 patients. A query population of 89,963 HL patients with more than one face-to-face encounter within any two-year period during the query interval was established. Validated associated ICD-10 diagnoses were assessed within the Cosmos system. The query revealed that HL patients had a median age of 56, with a male predominance (51.8%), and 35% were diagnosed between the ages of 15 and 39. Staging information was available for only 10% of patients. The most common comorbid diagnoses defined by ICD-10 were essential hypertension (45.4%), hyperlipidemia (36.1%), anemia (32.1%), GERD (32.1%), shortness of breath (31.4%), fatigue (30.1%), non-HL (30%), cough (26.3%), and anxiety (25.6%). Further assessment of hypertension and associated disorders was conducted by querying Epic grouper terms in comparison to the general Cosmos population. The HL population had a higher prevalence of hypertension (46.1% vs. 24.5%), chronic kidney disease (14.9% vs. 5%), hypertensive renal disease (10.1% vs. 3.1%), hyperlipidemia (44% vs. 21.1%), coronary artery disease (20.7% vs. 6.2%), ischemic or unspecified stroke (4.4% vs. 1.6%), and myocardial infarction (9.6% vs. 2.8%). Notably, death dates were documented for 12.5% of the HL population (compared to 3% in the general Cosmos population), but cause of death information was limited (0.028%). EMR informatics presents a powerful tool for rapidly generating real-time observational data, which can inform focused studies and interventions. Such data is crucial for understanding trends in treatment-related morbidity and mortality in diseases like HL, which can impact future health in survivorship. This study suggests that hypertension and related disorders may be more prevalent in the HL population compared to the general Cosmos population, warranting further directed study and validation in the future.

Pregnancies and Childbirth Following Advanced-Stage Hodgkin Lymphoma Treatment with Brecadd or Beacopp in the Randomized Phase III GHSG HD21 Trial

INTRODUCTION The GHSG-HD21 trial in adult patients with newly diagnosed advanced-stage classical Hodgkin lymphoma (AS-cHL) compares BrECADD (Brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone) to eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone). Superior treatment-related morbidity (TRMB) and at least non-inferior efficacy of BrECADD with high progression-free survival (PFS) rates after three years were presented previously. Fertility following chemotherapy is a major concern for these mostly young AS-HL patients. Therefore, we analyzed pregnancies and childbirth rates reported in HD21. METHODS This international open-label phase III trial included adult patients aged ≤ 60 yrs with AS-cHL. Patients were randomized in a 1:1 ratio to PET2-guided 4-6 cycles of either eBEACOPP or BrECADD. PET2 and PFS events were assessed by blinded panel review. Frequency of pregnancies among patients or their partners were analyzed in all female patients below 40 years and male patients below 50 years included in the ITT cohort for the safety endpoint TRMB. Descriptive statistics were used to report pregnancy rates. Childbirth rates per year were compared to German population data for women between 18-40 years in the years 2016-2020, obtained from the German Federal Statistical Office (Destatis). The trial was registered at clinicaltrials.gov (NCT02661503) and conducted according to ICH-GCP guidelines. RESULTS Between July 2016 and August 2020, we enrolled 1,500 patients from 9 countries and 233 trial sites. The final cohort for this analysis comprised 1200 patients (496 women and 704 men; 80.1% of ITT). Baseline characteristics were well balanced between treatment arms and median follow-up for this analysis was 40 months. 55.6% of the patients had cryocpreservation prior to chemotherapy (46.1% women, 76.4% men). At time of this analysis, there were 126 reported pregnancies during follow-up. Data was incomplete in 25 cases, and these were excluded from analysis. Overall, 97 (9.1%) patients had at least one documented pregnancy; 38 (7.2%) and 53 (9.8%) in eBEACOPP and BrECADD arm, respectively. Nine patients had more than one pregnancy. Compared to eBEACOPP, pregnancy rates following BrECADD were higher in males (5.7% vs. 2.5%) and females (13.2% vs. 11.8%). 8.2% of patients with reported pregnancy made use of cryopreservation. 82.2% of all pregnancies resulted in childbirth and 17.9% ended early (4% due to induced abortion; 13.9% due to abortion). Among patients with reported childbirth, there was a greater proportion of female patients vs. partners of male patients (63.9% vs. 36.1%); otherwise there were no notable differences between baseline characteristics or total cycles of chemotherapy in patients with reported pregnancy compared to the rest of the cohort. Median time from last day of chemotherapy until date of birth was 32 months (range 4-57). In women between 18 and 40 years, the childbirth rate per year increased during the first two years after treatment (first year: 0.6% [CI95: -0.1-1.3]; second year: 4.4% [CI95: 2.4-6.3]) and were numerically above the population reference (6.51%) starting from the third year (third year: 8.8% [CI95: 5.9-11.7]; fourth year: 8.0% [CI95: 4.5-11.4]; fifth year: 7.8% [CI95: 2.9-12.8]). CONCLUSION We report high rates of pregnancy following chemotherapy in the HD21 trial; approximately one tenth of patients below age 40 (female) or 50 (male) in the HD21 trial have reported a pregnancy during follow-up. Compared to eBEACOPP, pregnancy rates were twofold higher in partners of men who received BrECADD and slightly higher in women. Notably, childbirth rates in women after the second year of follow-up were comparable to the German population. Together with unparalleled primary cure rates achieved with BrECADD, our data supports its use in young patients with a desire to have children.

Assessing out-of-pocket cost differences in treatment for Medicare-eligible patients with favorable prognosis early-stage Hodgkin lymphoma.

15 Background: In the treatment of favorable Hodgkin Lymphoma (HL), Level 1 evidence comparing combined modality therapy (CMT) with chemotherapy alone has persistently demonstrated that obviating radiation therapy (RT) worsens recurrence rates despite no significant overall survival difference. As there remains limited evidence on the granularity of the impact of insurance on HL treatment, this project disaggregates costs by insurance plans to enhance the transparency of out-of-pocket (OOP) cost estimations in Medicaid and/or Medicare-eligible (age 65+) patients. Methods: National Comprehensive Cancer Network guidelines were queried to assess the appropriate therapy for HL. Following initial adriamycin/bleomycin/vinblastine/dacarbazine (ABVD) chemotherapy x 2 cycles with Deauville 1-2 response on PET scan, CMT was defined as involved site RT (20 Gy / 10 fractions), while chemotherapy alone was defined as an additional ABVD x 2. Current Procedural Terminology and Healthcare Common Procedure Coding System codes identified treatments. OOP expenditures, deductibles, and copay/coinsurance were computed for Medicaid, Original Medicare, and Medigap Plan G plans via medicare.gov, medicaid.oh.gov, and cms.gov. Price estimates (from actual prices per insurance plan rather than claims data predictions) assume an Ohio hospital location (zip code = 44106) for all treatments. Total costs were calculated based on all treatments plus a 5-year follow-up (not adjusted for inflation). Treatment charges for chemotherapy alone include initial medical oncology office visit, cost of ABVD x 4, and infusion costs for 4 cycles. Additional treatment charges for CMT include initial radiation oncology consultation, treatment planning, dosimetry calculations, treatment device, simulation and verification, RT delivery, on-treatment visits, medical physics consultation, and annual TSH labs. Results: With Original Medicare plans, patients are faced with an OOP cost of 20% for Medicare Part B claims with no cost cap for approved procedures after the deductible. As such, patients are faced with a total 6-year charge of $1,928.95 for chemotherapy alone, and $2,385.28 for CMT. Under Medigap Plan G, patients encounter an OOP charge of $1,151.14 for chemotherapy alone and $1,176.34 for CMT. Medicaid beneficiaries (assuming all treatments are approved by Medicaid) face no OOP expenses for both treatment plans, as all expenses are covered without limit. Conclusions: By comparing OOP costs between Medicare and Medicaid plans, this model improves cost transparency in the treatment of favorable early-stage HL. Our findings indicate that omitting RT in favor of chemotherapy alone yields a cost savings of 2-24% at a 5-year follow-up. Further studies are required to assess whether these savings compensate for the inferior outcomes achieved by omitting RT in this patient population.

Response Evaluation with PET/CT and Radiotherapy Planning in Hodgkin Lymphoma Treatment

Response Evaluation with PET/CT and Radiotherapy Planning in Hodgkin Lymphoma Treatment

Improved survival of children and adolescents with classical Hodgkin lymphoma treated on a harmonised protocol in South Africa.

Historic South African 5-year overall survival (OS) rates for Hodgkin lymphoma (HL) from 2000 to 2010 were 46% and 84% for human immunodeficiency virus (HIV)-positive and HIV-negative children, respectively. We investigated whether a harmonised treatment protocol using risk stratification and response-adapted therapy could increase the OS of childhood and adolescent HL. Seventeen units prospectively enrolled patients less than 18years, newly diagnosed with classical HL onto a risk-stratified, response-adapted treatment protocol from July 2016 to December 2022. Low- and intermediate-risk patients received four and six courses of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD), respectively. High-risk patients received two courses of ABVD, followed by four courses of cyclophosphamide, vincristine, prednisone, and dacarbazine (COPDac). Those with a slow early response and bulky disease received consolidation radiotherapy. HIV-positive patients could receive granulocyte colony-stimulating factor and less intensive therapy if stratified as high risk, at the treating clinician's discretion. Kaplan-Meier survival analysis was performed to determine 2-year OS and Cox regression to elucidate prognostic factors. The cohort comprised 132 patients (19 HIV-positive, 113 HIV-negative), median age of 9.7years, with a median follow-up of 2.2years. Risk grouping comprised nine (7%) low risk, 36 (27%) intermediate risk and 87 (66%) high risk, with 71 (54%) rapid early responders and 45 (34%) slow early responders, and 16 (12%) undocumented. Two-year OS was 100% for low-risk, 93% for intermediate-risk, and 91% for high-risk patients. OS for HIV-negative (93%) and HIV-positive (89%) patients were similar (p=.53). Absolute lymphocyte count greater than 0.6×109 predicted survival (94% vs. 83%, p=.02). In the first South African harmonised HL treatment protocol, risk stratification correlated with prognosis. Two-year OS of HIV-positive and HIV-negative patients improved since 2010, partially ascribed to standardised treatment and increased supportive care. This improved survival strengthens the harmonisation movement and gives hope that South Africa will achieve the WHO Global Initiative for Childhood Cancer goals.

Low Dose Involved Site Radiotherapy as Single Modality Treatment for Early-Stage Nodular Lymphocyte Predominant Hodgkin Lymphoma.

Involved site radiotherapy as a single modality is considered standard of care for early-stage non-bulky nodular lymphocyte predominant Hodgkin's Lymphoma (NLPHL) with excellent rates of local control and overall survival. Guidelines suggest a dose of 30 Gy in conventional fractionation, however NLPHL has an indolent course and clinically behaves likes a low-grade lymphoma. Given the good prognosis NLPHL has been treated as low grade non-Hodgkin's lymphoma with a dose of 24 Gy in 12 fractions. Eleven patients with stage I-II non-bulky NLPHL treated with involved site radiotherapy alone to a dose of 24 Gy in 12 fractions between 2010 and 2021 were respectively identified and reviewed. Data on toxicity, post treatment PET, relapse and site of relapse were recorded from multidisciplinary meetings records and regular six monthly clinic reviews. Mean patient age was 45 (range 25-74), 9 were male. 8 were classified as having Ann-Arbor stage IA disease, and the remaining 3 had IIA disease. All patients were prescribed 24 Gy in 12 fractions, 6 patients had 3D-conformal radiotherapy, 1 static IMRT and 4 VMAT. After a median follow up of 32 months (range 12-147) the overall response rate was 100% and all patients had complete metabolic response on PET scan, performed three months following the completion of radiotherapy. All patients remained disease free throughout the follow up period (PFS and OS 100%). There were no late toxicities reported. This is the largest reported series of NLPHL patients treated with low dose involved site modern radiotherapy. Patients had excellent local control rates and survival with no significant toxicity, supporting the use of 24 Gy in early-stage non-bulky disease.

Investigating PET Responses to Treatment in Nodular Lymphocyte-Predominant Hodgkin Lymphoma.

There is no standard treatment for nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). Although response by positron emission tomography (PET) for classic Hodgkin lymphoma (cHL) has allowed for response-adapted treatment, similar approaches for NLPHL have not been developed. This is in part due to the lack of data for PET response to treatment. Therefore, we sought to investigate PET responses to management for NLPHL. We retrospectively identified 47 patients who were diagnosed with or treated for NLPHL between 2001-2018 at a single institution and underwent a staging PET. We recorded clinical data and PET metrics for patients who received various forms of management, including chemotherapy (CT), radiation therapy (RT), combined modality therapy (CMT = CT+RT, with rituximab in a subset), rituximab monotherapy, and observation after excision. Metabolic response was scored according to the Deauville 5-point scale criteria, with complete metabolic response defined as a score 1-3. We identified 47 patients with median age of 26 (IQR = 17-50). They predominantly were male (74.5%) and had early stage (23.4% I, 36.2% II) versus advanced stage (29.8% III, 10.5% IV) NLPHL. The majority of patients had their immunoarchitectural pattern scored (n = 36, 76.6%), with typical pattern (A/B) being the most frequent type (58.3%). The median follow-up was 5.7 years (IQR = 2.3-9.3). Overall survival was 100% at 5 years and 92.3% at 10 years. Primary management included CMT (n = 10, 21.3%; with rituximab in a subset n = 1, 10.0%), CT alone (n = 22, 46.8%; with rituximab in a subset n = 5, 22.7%), RT alone (n = 8, 17.0%), rituximab alone (n = 3, 6.4%), and observation after excision (n = 4, 8.5%). On baseline PET, median SUVmax was 10.7 (range = 1.7-35.4). Of the 10 patients who received CMT, the complete metabolic response rates were 42.9% at interim-chemotherapy PET and 75% at post-chemotherapy PET, which improved to 100% after consolidative radiotherapy. There was no difference in complete metabolic response rate to chemotherapy for typical versus variant pattern (P = 0.60). Of the 22 patients who received CT alone, 66.7% had a complete metabolic response at the interim PET and 72.7% at the end of chemotherapy. For RT, rituximab alone, and observation, the complete metabolic response rates at median 3 months (range 1-5 months) after treatment were 87.5%, 66.7%, 75.0%, respectively. Based on our cohort, we found that patients with NLPHL had a lower complete metabolic response to CT (∼75%) compared to cHL (∼85-90%) and PET-response was improved following RT for those receiving CMT. There was no significant difference in PET-response for those with variant versus typical immunoarchitectural patterns. Our findings will allow for the development of PET response-adapted therapy for NLPHL.

Quality Analysis of Radiation Therapy for Hodgkin Lymphoma in the HD 16/17 Trials: A Final Report By the Reference Radiation Oncology Panel of the German Hodgkin Study Group

The HD 16 and 17 trials by the German Hodgkin Study Group (GHSG) have evaluated the use of consolidative radiotherapy (RT) in early-favorable and -unfavorable stage Hodgkin lymphoma (HL), respectively (1, 2). Quality of RT planning and execution is pivotal for treatment outcome in HL with protocol violations jeopardizing prognosis (3). Consequently, the present work aims at a decisive analysis of quality and dosimetry in the modern era. Random samples of 100 involved-field RT (IFRT) plans in HD16 and 176 plans in HD17 (134 involved-node RT (INRT) and 42 IFRT) were selected for analysis. Evaluation was performed systematically by the reference radiation oncology panel using pre-chemotherapy imaging, recommendation by the reference radiation oncology and RT planning imaging and graded as "correct", "minor" or "major deviation", respectively. RT doses to the target volume and organs at risks (OAR) were analyzed using dose-volume histograms. Median RT doses were 20 Gy (19.8 Gy-21.6 Gy) in HD16 and 30 Gy in HD17 (IFRT: 18-30.6 Gy, INRT: 14 Gy-40 Gy). Overall, 84.0%, 69.0%, and 76.1% of RT series in HD16, the IFRT-group of HD17 and the INRT-group of HD17, respectively, were planned correctly. The main reason for major deviation was an insufficient coverage of an involved region (11 %-14.3 %). There was no significant difference in quality between IFRT and INRT in HD17 (p = 0.418 for any deviations; p = 0.466 for major deviations). In comparison to previous GHSG studies in the respective stages, a significant increase in correct RT-series (p<0.001) and decrease in major deviations (p<0.001) occurred. However, doses to OAR varied individually with median values of 4.3 Gy (0.2 Gy-9.2 Gy), 4.7 Gy (0.2 Gy-15.2 Gy) and 3.8 Gy (0.0 Gy-16.0 Gy) for mean doses to the right lung, left lung and heart in HD16, respectively. Correspondingly, values were 9.8 Gy (0.3 Gy-20.0 Gy), 10.5 Gy (0.2 Gy-26.5 Gy) and 13.1 Gy (0.5 Gy-30.4 Gy) for mean doses to the right lung, left lung and heart in HD17, respectively. The size of the planning target volume decreased significantly with INRT compared to IFRT (median values: 1163.1 ml vs. 1464.3 ml; p = 0.043). However, only some OAR-parameters (V25 of the right and left lung, respectively, thyroid and spinal cord) showed significant differences between INRT and IFRT in HD17. The use of intensity-modulated techniques in HD 17 resulted in an increase in V5 and V10 of the lungs with a concomitant decrease in V20-V30. Quality of RT in the planning and treatment of HL has improved significantly with the latest GHSG study generation. Future analyses will focus on a further individualization of treatment fields.

Risk of Cardiac-Specific Mortality in Patients with Lymphoma Treated with Radiotherapy

The mainstays of treatment for Non-Hodgkin (NHL) and Hodgkin (HL) lymphoma are chemotherapy, radiotherapy (RT), or a combination of both. Thanks to improvements in treatment options many patients outlive their diagnosis by several decades. As treatments are de-intensified and cardiac sparing techniques have improved, the impact of RT on cardiac mortality should be re-visited. In this study, we sought to investigate the potential association between thoracic irradiation and cardiac-specific mortality (CSM) in patients with lymphoma. We hypothesized that receipt of RT would be associated with higher risk of cardiac death. The Surveillance Epidemiology and End Results (SEER) database was queried to identify all patients with HL and NHL with a thoracic primary site from 1975 to 2018. Kaplan Meier estimators were used to analyze cardiac-specific survival. Cohorts were balanced using inverse probability treatment weighing (IPTW). Hazard ratios were calculated using multivariate cox regression analysis. The following treatment eras were defined for analysis: pre-1995, 1995-2003, post-2003, to roughly correspond to the adoption of 3D conformal RT (3DCRT) and intensity-modulated RT (IMRT). We identified 10,602 patients, of which 8,088 (76%) had NHL and 2,514 (24%) had HL. Seventy-three percent of patients received chemotherapy and 38% received RT. Median follow up was 11.2 years. Forty-eight percent of patients were alive at last follow up, 6.6% had died from cardiac-specific causes, and 45% had died of other causes. Patients who received RT were had a lower risk of CSM (HR = 0.64, p < 0.01). However, IPTW survival analysis revealed no difference in the risk of cardiac death between the treatment cohorts (HR = 1.00, p = 0.99). Multivariate cox regression analysis identified female sex (HR = 0.73, p <0.01), age younger than 40 (HR = 0.27, p <0.01), and diagnosis after 1995 (HR = 0.31, p <0.01) to be associated with a lower CSM. In patients who received RT, we found that the risk of CSM was a higher (HR = 2.66, p <0.01) in those treated in the pre-1995 era and lower (HR = 0.32, p < 0.01) in the post-2003 era when compared to patients treated between 1995-2003. Additionally, receipt of RT was associated with a lower risk of all-cause mortality (HR 0.82, p<0.01). Our IPTW analysis shows that patients with thoracic lymphoma treated with RT have a similar risk of cardiac death to patients who did not receive RT, and an improved OS. Known cardiovascular risk factors like male sex and older age were associated with higher risk of cardiac death in patients receiving RT. We also found that patients treated with RT pre-1995 had higher CSM compared to those treated in 1995-2003 and those treated after 2003 had the lowest CSM, possibly in part attributable to the adoption of newer RT techniques. These findings may help clinicians counsel patients with lymphoma on the optimal modality of therapy and the possibility for late treatment effects in the modern era.

Current directions in the treatment of classical Hodgkin lymphoma.

Optimal management of patients who present with Hodgkin lymphoma continues to evolve. Most patients are cured with current treatment strategies, some but both short and long-term morbidity and mortality from treatment have particular relevance given the youth of the patient population. Combininations of targeted agents together with conventional chemotherapy have recently been investigated in phase 3 cliniial trials for advanced-stage Hodkgkin lymphoma, and have demonstrated improved efficacy compared with chemotherapy alone. These include both antibody-drug conjugates and PD-1 blockade. Treatment approaches have historically differed between pediatric and adult groups, but recent collaborations between adullt and pediatric groups via the NCTN mechanism have resulted in the successful completion of enrollment in an advanced-stage Hodgkin lymphoma and the opening of an early-stage trial that will enroll patients accross a broad age spectrum. Novel approachs incorporating targeted and immunomodulatory agents in the relapse setting are being actively investagated in the relapse setting as well.

Hodgkin Lymphoma Treatment Shifts to Immunotherapy

Hodgkin Lymphoma Treatment Shifts to Immunotherapy

EXABS-239-HL Treatment of Hodgkin Lymphoma in Older Patients

EXABS-239-HL Treatment of Hodgkin Lymphoma in Older Patients

POSTER: HL-122 Microbiota Changes in Hodgkin and Non-Hodgkin Lymphoma Treatment: Assessment With Il-17 and Il-12 Levels

POSTER: HL-122 Microbiota Changes in Hodgkin and Non-Hodgkin Lymphoma Treatment: Assessment With Il-17 and Il-12 Levels

HL-122 Microbiota Changes in Hodgkin and Non-Hodgkin Lymphoma Treatment: Assessment With Il-17 and Il-12 Levels

HL-122 Microbiota Changes in Hodgkin and Non-Hodgkin Lymphoma Treatment: Assessment With Il-17 and Il-12 Levels