Prognostic value of baseline metabolic tumor volume in children and adolescents with intermediate-risk Hodgkin lymphoma treated with chemo-radiation therapy: FDG PET parameter analysis in a subgroup from COG AHOD0031

Abstract

Background:

Positron emission tomography (PET)-based measures of baseline total-body tumor burden may improve risk stratification in intermediate-risk Hodgkin lymphoma (HL).

Materials and Methods:

Evaluable patients were identified from a cohort treated homogeneously with the same combined modality regimen on the Children’s Oncology Group AHOD0031 study. Eligible patients had high-quality baseline PET scans. Metabolic tumor volume (MTV) and total lesion glycosis (TLG) were each measured based on 15 thresholds for every patient. Univariate and multivariable Cox regression and Kaplan-Meier survival analyses assessed for an association of MTV and TLG with event-free survival (EFS).

Results:

From the AHOD0031 cohort (n=1,712), 86 patients were identified who i) were treated with 4 cycles of ABVE-PC chemotherapy followed by involved field radiotherapy and ii) had a baseline PET scan that was amenable to quantitative analysis. Based on univariate Cox regression analysis, 6 PET-derived parameters were significantly associated with EFS. For each of these, Kaplan-Meier analyses and the log-rank test were used to compare patients with highest tumor burden (i.e. highest 15%) to the remainder of the cohort. EFS was significantly associated with all 6 PET parameters (all P<0.029). In a multivariable model controlling for important coviariates including disease bulk and response to chemotherapy, MTV_2BP was significantly associated with EFS (P=0.012).

Conclusion:

Multiple baseline PET-derived volumetric parameters were associated with EFS. MTV_2BP was highly associated with EFS when controlling for disease bulk and response to chemotherapy. Incorporation of baseline MTV into risk-based treatment algorithms may improve outcomes in intermediate-risk HL.

Introduction

Hodgkin lymphoma (HL) in children and adolescents is highly curable, with a 5-year overall survival rate of >90%^1–3. Therefore, minimizing late treatment-related morbidity, such as secondary malignant neoplasms and cardiovascular disease^4–10, is critical. Modern treatment strategies focus on a risk-adapted approach that aims to reduce the incidence of late effects, while maintaining high cure rates^11–17. These regimens individualize therapy for each patient based upon pre-treatment prognostic factors and interim evaluations of disease response. Some features used for risk stratification, such as disease stage and bulk, are surrogates of tumor burden.

With advances in diagnostic imaging, it has become possible to measure tumor burden more directly. ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scans have become the standard modality for staging and response assessment in HL^18,19. In addition, FDG PET/CT scans can be used to quantify the 3-dimensional lymphoma volume. Metabolic tumor volume (MTV), one quantitative PET parameter, is defined as the total volume of disease with FDG uptake that exceeds a certain threshold. Total lesion glycolysis (TLG), another quantitative PET parameter, is calculated as the product of the MTV and the mean standardized uptake value (SUV_mean) of that MTV. A high total-body tumor burden, defined by these parameters, is associated with poorer prognosis in adults with various lymphomas, including HL^20–29. We hypothesized that these parameters would be associated with oncologic outcomes in children and adolescents with HL, as well. We explored the prognostic value of quantitative FDG PET/CT parameters in a subset of patients with intermediate-risk HL who were treated on the Children’s Oncology Group (COG) AHOD0031 trial.

Methods

Patients

This exploratory analysis of baseline FDG PET/CT images included a subset of patients who were treated on the multi-center COG AHOD0031 trial. This phase III study enrolled patients between 2002 and 2009 who were <22 years of age and had newly diagnosed, intermediate-risk HL (Ann Arbor stages IB, IAE, IIB, IIAE, IIIA, IVA with or without bulk; IA or IIA with bulk)¹³. Institutional Review Board approvals were obtained.

According to the COG AHOD0031 protocol¹³, patients received 2 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC) and then underwent early response evaluation by CT scan: patients with ≥60% reduction in the product of the perpendicular diameters (PPD) on CT were considered rapid early responders (RERs), whereas those with <60% reduction in the PPD were considered slow early responders (SERs). RERs received 2 more cycles of ABVE-PC and then were evaluated by PET/CT. They were considered to have achieved a complete response (CR) if they had an ≥80% reduction in the PPD and negative findings on PET at this timepoint. Among RERs, those with a CR were randomly assigned to involved field radiotherapy (IFRT) or observation, and those with less than a CR were non-randomly assigned to IFRT. SERs were randomly assigned to receive 2 more cycles of ABVE-PC with or without 2 cycles of dexamethasone, etoposide, cisplatin, and cytarabine (DECA). All SERs were assigned to receive IFRT.

The current study included a subset of patients who (1) were treated with 4 cycles of ABVE-PC and 21 Gy IFRT and (2) had a high-quality baseline ¹⁸F-FDG PET/CT scan that was amenable to quantitative analyses. Patients were included only if they had received 4 cycles of ABVE-PC and IFRT to remove the confounding effect of treatment regimen. From the 1,712 total patients who were eligible for AHOD0031, 50 were randomly selected from each of 3 different response groups: (1) RERs with a CR randomly assigned to IFRT, (2) RERs with less than a CR nonrandomly assigned to IFRT, and (3) SERs with no DECA augmentation nonrandomly assigned to IFRT. Among these 150 patients, 86 had baseline imaging that was amenable to quantitative PET analyses (Figure 1). This subset comprised our study population.

Figure 1.

CONSORT diagram.

PET/CT Protocol

Functional imaging methodologies evolved over the AHOD0031 study period from ⁶⁷Ga-Gallium scans, to PET scans alone, to PET/CT scans. Imaging studies were selected based on their availability at participating institutions.

The AHOD0031 protocol provided guidelines to standardize PET acquisition. Patients fasted for ≥4 hours prior to the injection of FDG. Plasma glucose was checked to confirm that the patient was not hyperglycemic, then FDG was administered intravenously at a dose of 0.125–0.200 mCi/kg (minimum dose 2.0 mCi, maximum dose 20.0 mCi). Images were obtained 45–60 minutes after ¹⁸F-FDG injections. The use of a dedicated PET camera and a 3D acquisition technique was preferred. FDG studies were processed by filtered back projection or an iterative reconstruction algorithm. Attenuation correction was performed. SUV measurements were normalized for body surface area.

Image Analysis

PET/CT scans were anonymized at the institutions where they were performed, transferred to a central facility, and uploaded for evaluation on the MIMVista^™ platform (version 5.2; MIM Software Inc. Cleveland, OH). For the current study, images were independently analyzed by two nuclear medicine experts (AC and JK), and discrepant cases were consensually discussed with a third expert reader (SC). All readers were blinded to clinical outcomes. Initial qualitative analysis included visual identification of all nodal disease above and below the diaphragm with increased size on CT and/or abnormal metabolic activity on PET. Then, quantitative PET parameters were collected as follows:

• maximum SUV (SUV_max): SUV of the single pixel with the highest FDG uptake within the lymphoma volume

• peak SUV (SUV_peak): average SUV of a 1.2 cm³ sphere in the region with the highest FDG uptake within the lymphoma volume³⁰

• MTV: whole-body lymphoma volume with FDG uptake exceeding a specified SUV threshold (thresholds defined below)

• TLG: whole-body MTV multiplied by the SUV_mean of that MTV

A total of 32 PET parameters, including 30 volumetric parameters (MTV and TLG each based upon 15 thresholds) and 2 SUVs (SUV_max and SUV_peak), were evaluated. The optimal threshold for tumor segmentation is unknown, so multiple thresholds were used to define the MTV and TLG in each patient, and we explored which were the most prognostic. We utilized:

• relative thresholds ranging from 20% to 60% of the SUV_max and SUV_peak at increments of 10% (i.e. 20%, 30%, 40%, 50%, and 60%)

• fixed thresholds of SUV 2.5 and 3.0

• reference-based thresholds derived from the average activity of the liver (Lv) and blood pool (BP). The two Lv thresholds were defined as “1.5 × Lv_mean activity” and “1.5 × Lv_mean activity + 2SD” measured in a 3 cm³ spherical VOI within the right hepatic lobe. The BP threshold was defined as “2 × BP_mean” measured in a 1 cm³ spherical VOI within descending thoracic aorta³⁰.

For volumetric analyses, spherical volumes of interest (VOIs) were drawn manually to include all lymphomatous involvement on the FDG PET images, and isoactivity contours were automatically applied in the VOIs. The edges of all lymphoma VOIs were adjusted to exclude neighboring normal structures with FDG uptake. Sites demonstrating increased background activity (eg. heart, liver, brain) were carefully delineated and often subjected to consensual review among readers.

Bulk disease was defined as a mediastinal mass with a diameter greater than 1/3 of the thoracic diameter on an upright posterior-anterior (PA) chest radiograph (CXR) or an extra-mediastinal nodal aggregate >6 cm in the longest transverse diameter on axial CT³¹.

Statistical analysis

The primary endpoint was event-free survival (EFS), defined as the time from trial enrollment to an event including progression, recurrence, second malignant neoplasm, or death. All 32 PET-derived parameters were screened for an association with EFS by univariate Cox regression analysis. Kaplan-Meier analyses were performed to estimate EFS, and the log-rank test was used to compare EFS between risk groups. Patients were stratified according to high vs. low MTV or TLG based on the 85% quantile (i.e. the patients with the highest 15% of values were compared to the remainder of the cohort). We selected the 85% quantile, because ~15% of patients were expected to develop relapsed/refractory disease, and our goal was to identify these patients with the highest risk disease. Receiver operating characteristic (ROC) analyses were used to determine the sensitivity and specificity of PET parameters for predicting EFS. Multivariable Cox regression analyses included all predictors of interest and used stepwise selection to identify significant factors. For multivariable analyses, variables with P<0.2 remained in the model and those with P<0.05 were considered significant. Patient and disease variables were compared between risk groups using the Chi-square test or Fisher’s exact test for categorical variables and t-test for continuous variables. All statistical analyses were performed with SAS (version 9.4, SAS institute Inc., Cary, NC).

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Results

Patient and Disease Characteristics

Eighty-six pediatric and adolescent patients with intermediate-risk HL who were treated with 4 cycles of ABVE-PC and IFRT were included. Their characteristics are summarized in Table 1. Of these 86 patients, there were 29 (33.7%) RERs with CR, 33 (38.4%) RERs without CR, and 24 (27.9%) SERs. Seventy-one patients (82.6%) had bulky disease; 34 (39.5%) had a large mediastinal mass, and 56 (65.1%) had a large extra-mediastinal mass. At a median follow-up of 79.4 months, 9 cases of relapse/progression (10.5%) and 1 death (1.2%) were observed.

TABLE 1.

Patient characteristics

Parameters		N=86	%
Age, years	Median (range)	14.5 (4.5 – 20.1)
Age	>18 years	13	15.1
Gender	Male	43	50.0
Ann Arbor stage	I	4	4.7
	II	53	61.6
	III	18	20.9
	IV	11	12.8
Histology	Nodular sclerosis	73	84.9
	Mixed cellularity	5	5.8
	Lymphocyte predominant	5	5.8
	Unknown/unreported	3	3.5
B symptoms	Present	12	14.0
Large mediastinal adenopathy	MMR > 0.33	34	39.5
	MMR ≤ 0.33	48	55.8
	Unknown/unreported	4	4.7
Extra-mediastinal nodal aggregate	> 6 cm	56	65.1
	≤ 6 cm	30	34.9
Bulky disease	Present	71	82.6
	Absent	15	17.4
Response to chemotherapy	RER/CR	29	33.7
	RER/<CR	33	38.4
	SER	24	27.9

MMR, Mediastinal mass ratio; RER, Rapid early responder; CR, Complete remission; SER, Slow early responder

Selection of PET Parameters

Each patient’s total-body metabolic disease burden was quantified using MTV (the lymphoma volume with an SUV exceeding a specified threshold) and TLG (the MTV multiplied by the SUV_mean of this MTV). The optimal threshold for tumor segmentation is unknown. Therefore, multiple thresholds were used to define the MTV and TLG for each patient, as defined above, and we explored which of these were the most prognostic in this cohort. All 32 PET-derived parameters were screened for an association with EFS by univariate Cox regression analysis. Total-body MTV based on 4 thresholds (MTV_20%SUVmax, MTV_1.5Lv, MTV_1.5Lv+2SD, and MTV_2BP) and TLG based on 2 thresholds (TLG_{60% SUVmax} and TLG_2BP) were significantly associated with EFS.

Kaplan–Meier Survival Analyses

At a median follow-up of 79.4 months, the 5-year EFS rate was 87.9 % (95% CI: 79.8%−96.0%) for the complete cohort. We further explored the association of EFS with each of the 6 PET parameters that was identified by univariate Cox regression analysis (MTV_20%SUVmax, MTV_1.5Lv, MTV_1.5Lv+2SD, MTV_2BP, TLG_60%SUVmax and TLG_2BP). Patients were stratified into high vs. low MTV or TLG groups as defined by the 85% quantile: for each parameter, patients with the highest 15% of values were compared to the remainder of the cohort. According to these analyses, all 6 PET parameters were significantly associated with EFS (all P<0.029; Table 2). The greatest difference in EFS between the high vs. low tumor burden groups was observed for MTV_2BP (P<0.0001; Table 2, Figure 2).

TABLE 2.

PET parameters significantly associated with EFS. High vs. low MTV and TLG groups were defined by the 85% quantile.

Parameter	5-year EFS (+/− SE), high value	5-year EFS (+/− SE), low value	P-value
MTV20%	68% +/− 17%	91% +/− 4%	0.0160
MTV1.5Lv	62% +/− 14%	93% +/− 4%	0.0011
MTV1.5Lv + 2SD	62% +/− 14%	93% +/− 4%	0.0011
MTV2BP	54% +/− 15%	94% +/− 3%	<0.0001
TLG60%	69% +/− 14%	91% +/− 4%	0.0291
TLG2BP	62% +/− 14%	93% +/− 4%	0.0011

Figure 2.

Kaplan-Meier curves showing event-free survival of the study cohort stratified according to MTV_2BP. The MTV_2BP+ sub-cohort had the highest 15% of MTV_2BP values; the MTV_2BP- sub-cohort had the lowest 85% of MTV_2BP values.

ROC Analyses

We assessed the specificity and sensitivy of each PET parameter for identifying 5-year EFS. For MTV_20%SUVmax, MTV_1.5Lv, MTV_1.5Lv+2SD, MTV_2BP, TLG_60%SUVmax and TLG_2BP, the specificity was 88%, 89%, 89%, 91%, 88%, and 89%, respectively. The sensitivity was 40%, 50%, 50%, 60%, 40%, and 50%, respectively. The sensitivity and specifity of all 32 PET parameters are provided in Supplemental Table 1.

Multivariable Analysis

A multivariable Cox regression model was performed that included age, race, sex, Ann Arbor stage, histology, B symptoms, large mediastinal mass, large extra-mediastinal nodal aggregate, bulky disease, number of involved sites, disease response (ie RER/CR vs. RER/non-CR vs. SER), the 6 selected PET parameters, and MTV_40%SUVmax. We included MTV_40%SUVmax, even though it was not significantly associated with EFS on univariate analysis, because a threshold of 41% is used commonly in the literature³². The final model included only those variables with a P-value <0.2: age, race, bulky disease, large extra-mediastinal nodal aggregate, disease response to chemotherapy, MTV_2BP, TLG_60%SUVmax, and TLG_2BP (Table 3). In this multivariable analysis, MTV_2BP was significantly associated with EFS (hazard ratio (HR) = 60.5; 95% CI 2.50–1464; P=0.012) when controlling for other prognostically important covariates, including disease bulk and response to chemotherapy.

TABLE 3.

Multivariable analysis

Parameter	Hazard Ratio (95% CI)	P-value
MTV2BP	60.5 (2.50–1464)	0.012
TLG60%SUVmax	5.2 (0.66–40)	0.117
TLG2BP	0.04 (0.001–1.8)	0.098
Age	1.3 (0.95–1.9)	0.103
Race (ref: White)	Black: 0
	Other: 30.8 (1.3–758)	0.111
Bulky disease	33 (1.1–972)	0.042
Large extra-mediastinal nodal aggregate	0.05 (0.003–1.01)	0.051
Disease response (reference SER)	RER/<CR: 0.04 (0.002–0.75)	0.045
	RER/CR: 0.17 (0.03–0.91)

Characteristics Associated with MTV_2BP

Clinical and pathologic factors were compared between the high and low MTV_2BP groups as defined by the 85% quantile (Table 4). A high MTV_2BP was significantly associated with a higher Ann Arbor stage (P=0.005). Aditionally, all patients with a high MTV_2BP had bulky disease.

TABLE 4.

Comparison between the low and high MTV_2BP groups

Parameters	Low MTV2BP	High MTV2BP	P-value
	(n=73)	(n=13)
Age, years (mean+/−sd)	14.5 +/− 3.3	15.6 +/− 2.9	0.275
Gender			0.367
Male	35 (48%)	8 (62%)
Female	38 (52%)	5 (38%)
Ann Arbor stage			0.005
I	4 (6%)
II	50 (68%)	3 (23%)
III	12 (16%)	6 (46%)
IV	7 (10%)	4 (31%)
Histology			0.436
Nodular sclerosis	60 (82%)	13 (100%)
Mixed cellularity	5 (7%)
Lymphocyte predominant	5 (7%)
Unknown/unreported	3 (4%)
B symptom			0.115
Absent	61 (84%)	13 (100%)
Present	12 (16%)
Mediastinal mass			0.181
MMR ≤ 0.33	43 (59%)	5 (39%)
MMR > 0.33	26 (36%)	8 (61%)
Unknown/unreported	4 (5%)
Extra-mediastinal nodal aggregate			0.109
≤ 6 cm	28 (38%)	2 (15%)
> 6 cm	45 (62%)	11 (85%)
Bulky disease			0.072
No	15 (21%)
Present	58 (79%)	13 (100%)
Response to chemotherapy			0.644
RER/CR	25 (34%)	4 (31%)
RER/<CR	29 (40%)	4 (31%)
SER	19 (26%)	5 (38%)

MMR, Mediastinal mass ratio; RER, Rapid early responder; CR, Complete remission; SER, Slow early responder

Discussion

Most patients with HL will be cured by modern therapy, so minimizing the late effects of treatment is critical. Recent studies have aimed to tailor treatment, so patients with the most favorable prognoses receive less intensive therapy than those with a higher risk of developing relapsed or refractory disease³³. The goal of risk-adapted therapy is to minimize toxicity and maximize disease control. One factor that has been used routinely for risk stratification is various measures of baseline tumor burden. These measures have evolved with time. First, the Ann Arbor staging system dichotomized HL as bulky or non-bulky based on standing PA CXR measurements. In the 1989 Cotswolds revision of the Ann Arbor staging system, large masses outside of the mediastinum, defined by axial measurements, were incorporated into the definition of bulk³⁴. As CT software evolved to allow reconstruction of anatomic images in 3 dimensions, size measurements in the cranial-caudal dimension, as well as the axial dimension, were associated with prognosis³⁵. All of these factors were indirect measures of tumor burden. Most recently, the routine use of PET/CT in HL has enabled direct quantification of the total-body metabolic disease burden, with measures such as MTV and TLG. We hypothesized that such parameters would improve risk stratification and, thus, may contribute to risk-based individualization of therapy.

We found that PET-derived volumetric measures of baseline total-body tumor burden were significantly associated with EFS in pediatric and adolescent patients treated for intermediate-risk HL with chemo-radiation therapy. In addition, pre-treatment MTV was associated with classical prognostic factors. For example, MTV_2BP was significantly associated with Ann Arbor stage. Additionally, all patients with high MTV_2BP values also had anatomic disease bulk, as defined by CXR and/or CT scan. These findings are not surprising, because MTV, disease stage, and bulk are all measures of tumor burden. Importantly, however, MTV_2BP was significantly associated with EFS, even when controlling for bulk, as well as for disease response to chemotherapy, on multivariable analysis. These two factors, bulky disease and early response to chemotherapy, are used in current trials to guide risk-adapted treatment. Thus, our findings suggest that baseline PET measures of metabolic tumor burden may provide additional prognostic information and may improve risk stratification for individualized treatment regimens. We found that PET volumetric parameters were highly specific for identifying patients whose disease did not progress, so they may be useful for selecting patients in whom therapy may be de-escalated.

This study adds to a growing body of evidence demonstrating the prognostic value of baseline MTV in HL. For example, Cottereau et al. found that baseline MTV was highly associated with progression-free survival (PFS) and overall survival (OS) in a cohort of 258 adult patients with early-stage HL who were treated on the EORTC H10 trial. Five-year PFS and OS were 92% and 98% in the low MTV group vs. 71% and 83% in the high MTV group, respectively²⁴. Likewise, Akhtari et al. evaluated a cohort of 267 adults with early-stage HL and found that baseline MTV and TLG were significantly associated with freedom from progression and OS²⁵. In both studies, MTV enabled more accurate stratification than conventional risk factors. MTV has been explored in children and adolescents with HL, as well. For example, in a retrospective analysis of 50 patients with HL who were treated according to the EuroNet-PHL-C1 study, high MTV was significantly associated with inadequate response to induction chemotherapy³⁶. Thus, the results of multiple studies, inclusive of several hundred patients in total, suggest that baseline MTV predicts prognosis and can potentially aid in accurate risk stratification in HL.

We found that volumetric parameters better predicted outcome than conventional PET parameters such as SUV. This finding has been reported by other researchers, as well. As one example, in 57 patients treated for HL or non-HL, Bouallegue et al. identified no association between early metabolic response and SUV_max, SUV_mean, or SUV_peak; conversely, volumetric measures of baseline tumor burden, including MTV, were highly associated with early metabolic response³⁷. Similarly, in 50 pediatric patients with HL, Rogasch et al. found that high MTV significantly out-performed SUV_max, SUV_mean, and SUV_peak in predicting inadequate early response to chemotherapy³⁶. Volumetric measures may better predict oncologic outcome than SUV because they reflect not only the metabolic activity, but also the total anatomic burden of disease.

One factor that has prevented MTV from being used in routine clinical practice to date is that there is no consensus regarding the best and most reproducible technique for tumor segmentation. Several methods are available, including quantification of the volume of disease with an SUV greater than a fixed absolute threshold (ex. SUV 2.5), a fixed relative threshold (ex. 41% of the tumor SUV_max), or a background-based threshold (ex. Lv or BP). Each of these approaches has advantages and disadvantages³⁸. We explored several thresholds in each of these 3 categories. In our cohort, MTV_2BP was the most highly associated with EFS. However, other thresholds have been used more commonly by other groups, including a fixed absolute threshold of SUV 2.5 and relative threshold of 41% of the tumor SUV_max^24,25,38. Further research is needed to determine the optimal approach and to standardize the definition of MTV.

We acknowledge the limitations of this study. First, the findings were obtained from a single cohort and require external validation to be used for clinical decision-making. Second, our statistical analyses were limited by the small number of events and small number of patients, particularly if the cohort was divided into subgroups (RER/CR, RER/non-CR, SER). In addition, we were limited in the number of high-quality PET/CT images that were amenable to quantitative analyses, because functional imaging evolved over the course of the AHOD0031 study period from ⁶⁷Ga-Gallium, to PET alone, to current, state-of-the-art PET/CT imaging that is available as DICOM files. Only these most advanced PET/CT images were amenable to quantitative analyses, so not all patients treated on AHOD0031 were evaluable for our exploratory study. To overcome this limitation, we will perform similar analyses in a more contemporary cohort treated on AHOD1331. In addition, a machine learning approach may be applied in future studies.

Current research efforts will contribute to the use of quantitative PET parameters not only in large multi-center clinical trials, but also in routine clinical management. As described above, the optimal approach for MTV segmentation is an area of active study. Advanced algorithms have become available, and current research efforts aim to standardize measurements and maximize automation to improve the ease and speed of acquisition³⁸. We predict that once these technical aspects have been resolved, PET-based volumetric parameters will become the routine measure of baseline disease burden that contribute to risk-based treatment strategies in HL.

Conclusion

Baseline metabolic tumor burden, as measured on pre-treatment PET scans, was significantly associated with EFS in children and adolescents with intermediate-risk HL who were treated homogeneously with 4 cycles of ABVE-PC and IFRT. MTV_2BP was significantly associated with EFS when controlling for anatomic bulk and disease response to chemotherapy, two factors that are used in current trials to guide risk-adapted treatment. These findings suggest that PET-based, volumetric measures of upfront total-body disease burden may improve risk stratification. Incorporation of baseline MTV into risk-based treatment algorithms has significant potential for improving clinical outcomes in HL.

Abbreviations:

ABVE-PC

Doxorubicin, Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide

AUC

Area Under the Curve

BP

Blood Pool

COG

Children’s Oncology Group

CR

Complete Response

CT

Computed Tomography

CXR

Chest X-Ray

DECA

Dexamethasone, Etoposide, Cisplatin, Cytarabine

EFS

Event-Free Survival

FDG

¹⁸F-fluoro-2-dexoxy-D-glucose

HL

Hodgkin Lymphoma

IFRT

Involved Field Radiation Therapy

Lv

Liver

MTV

Metabolic Tumor Volume

OS

Overall Survival

PA

Posterior-Anterior

PET

Positron-Emission Tomography

PFS

Progression-Free Survival

PPD

Product of the Perpendicular Diameters

RER

Rapid Early Response

ROC

Receiver Operating Characteristic

SER

Slow Early Response

SUV

Standardized Uptake Value

TLG

Total Lesion Glycolysis

VOI

Volume of Interest