Radiation target nomenclature for lymphoma trials: consensus recommendations from the National Clinical Trials Network groups

Abstract

Contemporary lymphoma radiation (RT) target volumes that rely on post-systemic therapy imaging lack standardized nomenclature. A forum of radiation oncology lymphoma leaders from NCTN groups (NRG, COG, SWOG, ALLIANCE, ECOG-ACRIN, CCTG) was convened and established standardized nomenclature for these volumes. ISRT includes the full cranial-caudal extent of pre-chemo disease and takes into account axial anatomical changes only. Residual site radiotherapy (RSRT) targets only the post-chemo CT-anatomical mass. Positron emission tomography (PET)-directed radiotherapy (PD-RT) exclusively targets PET-positive disease and includes 3 types. PET-directed involved site radiotherapy (pISRT) includes the superior-inferior aspect of the pre-chemo involved disease site(s) that remain(s) PET-avid on post-treatment imaging. PET-directed residual site radiotherapy (pRSRT) includes only the post-chemo CT-anatomical residual mass that contains the PET-avid lesion on post-treatment imaging, without including sites that achieved complete metabolic response. PET-directed residual PET radiotherapy (pRPRT) includes only the PET-avid focus, irrespective of the corresponding adjacent non-PET-avid CT-anatomical disease surrounding it.

Introduction

Radiation therapy (RT) has been an integral component in the treatment of lymphoma for decades. When RT was used alone for the treatment of lymphoma, specifically Hodgkin lymphoma (HL), the historical RT fields included total lymphoid irradiation, subtotal nodal irradiation, and extended field irradiation, such as a mantle field (1, 2). Doses prescribed to these large fields were sometimes up to 40–50 Gy (3). However, advancements in both systemic therapy and diagnostic imaging have revolutionized outcomes and prognosis allowing for significant reduction in RT volumes to include involved-field RT (IFRT) (4), and more recently involved-site RT (ISRT) (5) and involved-node RT (INRT) (6). Specifically, the advancement in staging lymphoma patients with ¹⁸F-FDG-positron emission tomography (PET)-computed tomography (CT) facilitated enhanced accuracy in RT target delineation and aided in identifying individual lymphoma targets, contributing to further RT field size reduction (7, 8). Modern doses prescribed to these smaller fields can be as low as 20–30 Gy following systemic therapy which leads to a significant decrease in RT toxicity without compromising its efficacy (3, 9).

Recently, several cooperative group lymphoma trials (AHOD1331 (10), S1826 (11), AHOD2131: NCT05675410, ANHL1931: NCT04759586, AHOD1822: NCT03407144, AHOD1721: NCT02572167) have embraced post-treatment +/− interim PET imaging to help design RT target volumes, especially for sites requiring higher doses or RT boost, leading to a departure from the traditional ISRT and INRT paradigms that rely mostly on pre-treatment imaging. These contemporary fields have been utilized independently or in conjunction with traditional ISRT. However, the absence of standardized nomenclature for these contemporary PET-directed RT volumes has created ambiguity and hindered the standardized adoption of these modern fields and concepts.

The primary objective of this consensus nomenclature is to simplify and standardize the contemporary RT volumes nomenclature across future National Clinical Trials Network (NCTN) lymphoma clinical trials.

Methods

To address this deficiency in nomenclature and establish uniformity across contemporary clinical trials within the NCTN, the NRG Hematologic Malignancies (HM) Working Group in collaboration with Center for Innovation in Radiation Oncology (CIRO) convened a forum of radiation oncology lymphoma leaders from all NCTN groups. Participants included representatives from NRG Oncology, the Children’s Oncology Group (COG), SWOG Cancer Research Network, Alliance for Clinical Trials in Oncology (Alliance), ECOG-ACRIN Cancer Research Group (ECOG-ACRIN), and Canadian Cancer Trials Group (CCTG). This forum was established to develop a standardized nomenclature for contemporary lymphoma RT volumes used in recent and ongoing NCTN lymphoma trials.

First, approval of the project was granted by the NRG HM “Core” Working Group and CIRO. Subsequently, two members of the NRG HM Working Group (BSH, OS) identified relevant NCTN-led lymphoma studies published in the past 5 years or those that are actively accruing or have completed accrual. This was achieved by searching ClinicalTrials.gov for NCTN member studies that began enrollment after 2012 (the year ISRT was published) using the following search criteria: “Lymphoma + NRG,” “Lymphoma + COG,” “Lymphoma + SWOG,” “Lymphoma + ECOG,” “Lymphoma + Alliance,” and “Lymphoma + CCTG”. Recently published studies were identified through PubMed’s advanced search, limited to the past 5 years, using the keywords “lymphoma” AND “radiation” AND “NRG” OR “COG” OR “ECOG” OR “SWOG” OR “CCTG”. Included studies focused on B-cell lymphomas or Hodgkin lymphoma and involved radiation therapy as an intervention. Excluded were studies not involving radiation therapy, those addressing T-cell lymphomas, any type of leukemia, myelomas, or other hematological malignancies not classified as B-cell or Hodgkin lymphomas, as well as studies using IFRT or those that were terminated or suspended. Additionally, one industry sponsored COG study that was not captured by our search criteria was identified by a COG member of the NRG HM Working Group. Since this effort is led in collaboration with CIRO, which is housed under NRG and tasked with standardizing the use of RT across the NCTN groups, the studies were limited to those under NCTN and thus within North America.

Once the studies were identified, the protocols were retrieved from the NCTN main website, cooperative group websites, published studies, or group’s representative. After obtaining the protocols, the RT target volumes were meticulously reviewed. The target fields described in these protocols were analyzed and categorized accordingly. Recognizing that target fields from different protocols might show slight variations in margin development when grouped together, these discrepancies were expressed as ranges in the summary. The findings were then presented to the NRG HM “Core” Working Group members in a virtual meeting. Following discussions, a draft of standardized nomenclatures for these contemporary lymphoma RT target volumes was developed and reviewed by the committee. Two follow-up virtual meetings were held for further discussion after each subsequent draft, supplemented by a series of emails and correspondence.

The nomenclature was then presented to the larger forum that included radiation oncology representatives from each of the NCTN lymphoma committees: NRG, COG, SWOG, Alliance, ECOG-ACRIN, and CCTG. Their input and suggestions were incorporated into a final draft, which was approved by all members.

Current Practice and Evolving Standards in Target Volume Delineation

The current utilized RT volumes are based on the ISRT target delineation guidelines defined by the International Lymphoma Radiation Oncology Group (ILROG) for HL (12) and NHL (13, 14). ISRT was developed to eliminate the prophylactic irradiation of regional uninvolved nodal sites used in IFRT, while providing more pragmatic volume delineation compared to INRT, which requires strict guidance that is unlikely to be practically implemented in North America, such as obtaining a baseline PET-CT scan in the treatment position and evaluation by a radiation oncologist prior to initiation of systemic therapy. Yet, ISRT volumes can be interpreted and implemented differently among providers depending on the correlation between the patient position in the pre-treatment diagnostic imaging study as compared to the radiation CT simulation imaging study, anatomic changes that may occur after chemotherapy, perceived risk of subclinical disease by the treating radiation oncologist, and concerns for dose to specific organs at risk. ISRT clinical target volumes (CTV) can vary substantially and include the cranial–caudal extent of initial disease involvement with an additional few cm extension, in its most extensive form, or the post-chemotherapy anatomic extent of disease only, in its least extensive form when critical structures, like the heart are in close proximity and could receive high doses (15, 16).

In order to further reduce toxicity and target volume variability associated with ISRT, some groups developed the concept of residual site radiotherapy (RSRT) volume (17, 18). ISRT takes into account post-chemotherapy response and anatomic changes in the axial dimension only and includes the full pre-chemotherapy extent of disease in the cranial-caudal dimension. In contrast, RSRT includes only the post-chemotherapy anatomical extent of disease that is greater than a certain size cutoff (as defined by specific protocols) that is visualized on the contrast-enhanced CT scan (17, 18) in both the axial and cranio-caudal dimensions (Figure 1). The RSRT volume may be much smaller than the ISRT volume and is very similar/identical to the ISRT post-chemotherapy gross tumor volume (GTV^postchemo) with a PTV margin.

Figure 1.

Hodgkin lymphoma female patient with 2 PET-avid disease sites (Blue-colored masses in the neck and mediastinum). Only CT imaging is utilized which shows residual CT-anatomic disease following systemic therapy in the neck and mediastinum (gray-black masses). Involved-site radiotherapy (ISRT) volume will include and follow the superior-inferior aspect of the pre-systemic therapy disease from the neck to the mediastinum, regardless of CT or PET response. Residual site radiotherapy (RSRT) volume is based on disease CT-response and will only include the residual CT-anatomic disease, independent of PET response, without following the superior-inferior aspect of the pre-systemic therapy disease.

The concepts of ISRT and RSRT do not rely on post-treatment PET imaging, a functional assessment tool that can further refine those volumes.

PET-directed radiotherapy (PD-RT)

The use of RT on most contemporary NCTN lymphoma clinical trials has been largely influenced by the PET-CT imaging findings at interim and/or the completion of therapy. Using interim or post-treatment PET imaging to help inform the radiation volumes is what is defined in this manuscript as PET-directed radiotherapy (PD-RT). Specifically, PD-RT utilizes the interim (iPET) and/or end-of-systemic therapy PET scans to better define sites at high risk of relapse, which may benefit from the addition of radiation therapy or escalating the dose of radiation therapy. As seen on most contemporary lymphoma clinical trials, regardless of the initial pre-systemic therapy sites of disease, PD-RT was used to target only sites with slow early response (SER) on iPET (if performed and indicated) and sites with partial (PR) or no response on end-of-systemic therapy PET scan either as a boost or for the entire RT treatment. PD-RT includes different types, as discussed in the next section, and can be used alone or as a boost in combination with ISRT based on the patient’s disease stage and the treatment setting on current and recently published NCTN clinical trials (AHOD1331 (10), S1826 (11), AHOD2131: NCT05675410, ANHL1931: NCT04759586, AHOD1822: NCT03407144, AHOD1721: NCT02572167).

Types of PD-RT

Our forum is defining three standardized PD-RT contouring volumes’ nomenclatures based on the various PD-RT fields used in contemporary lymphoma clinical trials. These volumes include 1) PET-directed involved site radiotherapy (pISRT), 2) PET-directed residual site radiotherapy (pRSRT), and 3) PET-directed residual PET radiotherapy (pRPRT), as depicted in Figures 2–3 and appendix p1–3. Examining these trials and the accompanying illustrations, it becomes evident that PD-RT volumes can be used alone or in conjunction with ISRT/RSRT, depending on the patient’s disease stage and treatment setting. Table 1 incorporates our nomenclature into the NCTN clinical trials that used/are using PD-RT, which will be further discussed below.

Figure 2.

Hodgkin lymphoma female patient with 2 PET-avid disease sites (Blue-colored masses in the neck and mediastinum). PET-CT imaging is utilized and shows, following systemic therapy, complete metabolic response in the neck with non-PET avid residual CT-anatomic mass (gray-black mass), and partial metabolic response in the mediastinum with small residual PET-avid focus (blue mass) on top of a larger non-PET avid residual CT-anatomic mass (gray-black mass). PET-directed involved-site radiotherapy (pISRT) volume will include and follow the superior-inferior aspect of the mediastinal pre-systemic therapy disease as it remained with PET-avidity. PET-directed residual site radiotherapy (pRSRT) will only include the PET-avid mediastinal CT-anatomic disease and will not cover the non-PET avid CT-anatomic neck disease. PET-directed residual PET radiotherapy (pRPRT) will only include the PET-avid focus and will not include the corresponding/adjacent non-PET avid CT-anatomic disease.

Figure 3.

Female patient with large mediastinal early-stage HL who had residual PET-avid mediastinal disease (Deauville 4) on the interim and end-of-systemic therapy PET scans. ISRT (blue contour) would target the whole region that had the initial pre-systemic therapy disease. pRSRT (green contour) would target the CT-anatomic residual mass on end-of-systemic therapy PET-CT and simulation CT scans that is harboring the PET-avidity and would NOT extend superiorly-inferiorly to cover areas where the initial disease was previously located but is no longer present. pRPRT (violet contour) would target only the PET-avid focus on the end-of-systemic therapy PET without including any of the residual CT-anatomic disease that is not PET-avid.

ISRT = Involved-site radiotherapy; pRSRT = PET-directed residual site radiotherapy; pRPRT = PET-directed residual PET radiotherapy; Dark blue contour = ISRT clinical tumor volume; Light blue contour = ISRT planning tumor volume; Light green contour = pRSRT clinical tumor volume; Dark green contour = pRSRT planing tumor volume; Violet contour = pRPRT clinical tumor volume; Purple contour = pRPRT planning tumor volume. Red contour = heart; pink contour = breasts.

Table 1.

Target volume nomenclature applied to the contemporary NCTN lymphoma trials utilizing PET/CT imaging.

Study	Population/Stage	Systemic Therapy	RT indications	RT Type
				ISRT	pISRT	pRSRT	pRPRT
AHOD1331	Pediatrics high-risk HL (IIB bulky, IIIB, IVA, IVB)	A(B)VE-PC +/− BV	Pre-chemo LMA	Xa
			SER on iPET		Xa		Xb
			PR on EST-PET
S1826	Pediatrics and adults stage III/IV HL	AVD + BV or Nivo	PR on EST-PET*			Xc	Xd
ANHL1931 (NCT04759586)	Pediatrics and adults PMBCL	DA-REPOCH, RCHOP, or RCHOP+RT +/− Nivo	RCHOP + RT	Xc		Xe
			PR or primary refractory disease
AHOD2131 (NCT05675410)	Pediatrics and adults stage I/II HL	ABVD +/− AVD, eBEACOPP or BV-Nivo	SER on iPET	Xf		Xg
			PR on EST-PET			Xh
AHOD1822 (NCT03407144)	CAYA stage I-II non-bulky with SER	ABVD + Pembro with AVD	SER on iPET	Xi		Xj
			PR on EST-PET
AHOD1721 (NCT02572167)	CAYA with relapsed/refractory HL	BV-Nivo +/− Bendamustine	R1 cohortk	Xc

Abbreviations: ISRT = involved-site radiotherapy; pISRT = PET-directed involved-site radiotherapy; pRSRT = PET-directed residual site radiotherapy; pRPRT = PET-directed residual PET radiotherapy. CAYA = children and young adults; HL = Hodgkin lymphoma; PMBCL = primary mediastinal B-cell lymphoma; SER = slow-early response; PR = partial response; iPET = interim PET; EST-PET = end-of-systemic therapy PET; LMA = large mediastinal adenopathy; ABVE-PC = doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide; BV = brentuximab vedotin ; ABVD = doxorubicin (adriamycin), bleomycin, vinblastine, dacarbazine; Nivo = Nivolumab; DA-REPOCH = dose adjusted rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin; RCHOP = rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone; eBEACOPP = escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone; Pembro = Pembrolizumab.

To better understand the different types of PD-RT, it is crucial to first delineate the primary distinction between ISRT/RSRT and PD-RT. ISRT and RSRT are independent of post-treatment PET imaging. ISRT primarily relies on the pre-treatment extent of the disease, while RSRT focuses on post-treatment CT-anatomic disease, irrespective of its PET response. In contrast, PD-RT is only feasible in the presence of interim or post-treatment PET imaging, directing its delivery exclusively to PET-positive disease, irrespective of the pre- and/or post-treatment disease that achieved complete metabolic response. The three types of PD-RT differ based on the volume surrounding the PET-avid region to be included.

The pISRT target volume includes and follows the superior-inferior aspect of the pre-systemic therapy involved lymph node site(s) or tissue(s) that continue(s) to harbor PET-avidity on the interim and/or end-of-systemic therapy PET scan. pISRT was used in advanced-stage disease trials to identify areas at highest risk of relapse that warrant local therapy. This was seen in AHOD1331 (10), where patients with SER after 2 cycles of systemic therapy received RT specifically targeting the lymph node regions displaying SER after completing the full course of systemic therapy, what we are defining here as pISRT. Therefore, when ISRT is used to treat only the lymph node regions/tissues that are PET-positive at iPET or following treatment, it is defined as pISRT.

The pRSRT target volume includes the post-systemic therapy CT-anatomical residual mass that contains the PET-avid lesion on the interim and/or end-of-systemic therapy PET scan without covering/including all the initial extent of involved lymph node(s) or extranodal site(s) as seen with ISRT or pISRT. In contrast to RSRT, pRSRT will not include residual CT-anatomic disease sites that achieved complete metabolic response and have no PET-avidity. pRSRT is being used as a boost following ISRT on AHOD2131, AHOD1822 and ANHL1931. This allows dose painting to areas at lower/higher risk of relapse, where areas with CR receive lower doses of RT and areas with SER/PR receive higher doses of RT. For instance, if the patient in figure 3 is enrolled in AHOD2131, a CTV^ISRT (blue contour) will encompass all pre-chemo and post-chemo disease and CTV^pRSRT (green contour) will encompass the CT-anatomical mass that contains the PET-avidity on interim and end-of systemic therapy PET. pRSRT is also being used for consolidation/salvage of residual PR disease on the S1826 study. Therefore, when RSRT is used to treat only residual CT-anatomic disease sites that are PET-positive following treatment, it is defined as pRSRT.

pRPRT target volume includes only the PET-avid focus. It is very similar to pRSRT in cases where the residual CT-anatomic mass is fully avid. However, it differs from pRSRT in cases where there is a large residual CT-anatomic mass (pRSRT volume) with only a small focus of residual PET avidity (pRPRT volume). The latter scenario is commonly seen in patients with large mediastinal mass who achieve PR to systemic therapy. pRPRT was used as a boost following pISRT on AHOD1331 and following pRSRT on S1826. For example, appendix p3 illustrates a patient with HL, who after completion of systemic therapy had a good response with residual PET-avid disease (Deauville 4) in the mediastinum. If this patient had advanced stage disease and was enrolled in the SWOG S1826 trial, PD-RT would be utilized to include a pRSRT volume (blue contour) that targets the CT-anatomic mass containing the PET avidity followed by a pRPRT boost volume (red contour) that targets the PET-avid lesion only. Therefore, RT volume targeting only the PET-positive focus irrespective of the corresponding adjacent CT-anatomic disease, is defined as pRPRT.

PD-RT as a sequential or simultaneous integrated boost to ¹⁸F-FDG avid residual disease

As mentioned earlier, PD-RT can be utilized either alone or as a boost following ISRT/RSRT, and some forms of PD-RT. When used as a boost, PD-RT can be applied as a sequential or simultaneous integrated (SIB) boost. In earlier cooperative group contemporary trials, sequential PD-RT boosts were used, such as pRSRT following ISRT on AHOD1822, and pRPRT following pISRT on AHOD1331. However, more recently, cooperative trials have allowed for sequential or SIB PD-RT boosts, such as pRSRT following ISRT on AHOD2131.

Radiation Therapy Target volumes

Imaging required for target delineation

ISRT fields will require fusion with the baseline, pre-systemic therapy PET-CT or PET-MRI scan and any additional CT scans to be used for delineating the targets. RSRT and PD-RT fields will require additional fusion with interim and/or end-of-systemic therapy PET-CT scans.

Target Volumes (Table 2)

Table 2.

Tumor volumes and target delineation definitions.

Gross Tumor Volumes (GTVs)	Clinical Tumor Volumes (CTVs)	Internal Tumor Volumes (ITVs)	Planning Tumor Volumes (PTVs)
GTV^prechemo = Disease prior to any treatment based on the baseline PET-CT or PET-MRI scans	CTV^ISRT = lymph nodes/tissues originally involved with lymphoma (i.e., GTV^prechemo) + a margin of 1.0 cm above and below GTV^prechemo	ITV = CTV with an added margin to account for variation in shape and motion within the patient	PTV = CTV or ITV with a geometric margin to account for geometric variation in daily setup (5–10 mm)
	CTV^pISRT = lymph nodes/tissues originally involved with lymphoma (i.e., GTV^prechemo) that still contain PET-avidity on iPET and/or EST-PET +/− a margin of 1.0 cm above and below GTV^prechemo
GTV^postchemo = Residual CT-anatomic disease ≥ 1cm* on EST +/− interim scans	CTV^RSRT = (GTV^postchemo) + (0–5mm)
GTV^PET+ = PET-avid lesion on iPET and/or EST-PET	CTV^pRSRT = (CT-anatomic mass that contains GTV^PET+) + (0–5mm)
	CTV^pRPRT = (GTVPET+) + (0–5mm#)

^*GTV^postchemo size cutoff might be different based on protocol.

^#Further expansions are justifiable and may be warranted per protocol.

Abbreviations: iPET = interim PET; EST-PET: end-of-systemic therapy PET; ISRT = involved-site radiotherapy; pISRT = PET-directed involved-site radiotherapy; RSRT = residual site radiotherapy; pRSRT = PET-directed residual site radiotherapy; pRPRT = PET-directed residual PET radiotherapy.

As the use of ISRT, RSRT, and the various PD-RT types is not mutually exclusive and can involve any or all of them, we provide below all the necessary contouring volumes for delineating ISRT, RSRT, and PD-RT fields.

1. Gross Tumor Volumes (GTV):

1. GTV^prechemo includes nodal and non-nodal tissue that was involved with lymphoma prior to any treatment based on the baseline PET-CT or PET-MRI scans and any other additional prechemotherapy imaging. This volume is used to assist in developing ISRT and pISRT volumes.

2. GTV^postchemo includes persisting imaging abnormalities seen on CT following completion of systemic therapy and includes the residual CT-anatomic mass (regardless of PET avidity) that is greater than a certain size cutoff (per protocol) on the end-of-systemic therapy +/− interim PET-CT scans. This volume is needed for ISRT, pISRT, RSRT and pRSRT.

3. GTV^PET+ includes persisting imaging abnormalities seen on PET following completion of systemic therapy and includes only the PET-positive focus, without the corresponding CT-anatomic mass, seen on end-of-systemic therapy PET +/− iPET. This volume is needed for pISRT, pRSRT and pRPRT. The quality of PET fusion and the spatial resolution of PET-CT may introduce uncertainty in localizing PET-avid lesions on CT-simulation scans. Lesions exhibiting ¹⁸F-FDG uptake visually greater than that of the liver are included within this volume and should be confined by the CT boundary. Additionally, in such cases, a more generous contouring of the GTV^PET+ may be necessary.

2. Clinical Target Volumes (CTV):

1. CTV^ISRT includes the lymph nodes/tissues originally involved with lymphoma (i.e., GTV^prechemo), but must take into account the reduction in axial diameter that has occurred with chemotherapy or immunotherapy. Delineation of the CTV^ISRT requires consideration of the expected routes of disease spread, the quality of pre-treatment imaging, and receipt of and response to systemic therapy, and is based on the ILROG ISRT guidelines for HL (12) and NHL (13). These can be subject to variation in interpretation from one physician to another (15, 16, 19). The CTV^ISRT expansion cannot be rigidly determined a priori as there can be considerable uncertainties inherent with GTV delineation due to inaccuracies in matching patient positioning and the variable internal anatomy shifts that change with disease volume and patient position between diagnostic and treatment positions. A margin of 1.0 cm above and below lymph nodes (GTV^prechemo) involving lymphoma is recommended. However, smaller margins may be appropriate, especially when the CTV extension substantially increases the dose to an organ at risk. This scenario may arise in cases where the initial disease was located, but is no longer present, at the level of critical organs at risk such as the parotid gland or the heart. Uncommonly, normal nodal tissue may be included in the CTV^ISRT if located between two anatomically close (i.e., within 2 cm) sites requiring RT that are going to be joined and treated as a single volume.

2. CTV^pISRT is the same as CTV^ISRT but would only include and follow the superior-inferior extent of the lymph nodes/tissues originally involved with lymphoma that still harbor PET-abnormality on interim and/or end-of-systemic therapy PET-CT scans.

3. CTV^RSRT is a 0–5 mm margin (per protocol) on the GTV^postchemo which includes the residual CT-anatomic abnormality seen on end-of-systemic therapy +/− interim PET-CT scans.

4. CTV^pRSRT includes the CT-anatomic abnormality (GTV^postchemo) that contains the PET avid disease (GTV^PET+) seen on end-of-systemic therapy +/− interim PET-CT scans with a 0–5 mm margin (per protocol).

5. CTV^pRPRT is a 0–5 mm margin on the GTV^PET+ which includes only the PET positive focus seen on end-of-systemic therapy PET +/− interim PET scans. Further expansions are justifiable and may be warranted per protocol.

3. Internal Target Volume (ITV):

The ITV encompasses the CTV with an added margin to account for variation in shape and motion within the patient. Respiratory motion, for example, will produce movement of the mediastinal structures, and an additional margin around the CTV is required to account for this. There are three different approaches for developing an ITV based on simulating the patient with a 4D-CT scan, breath hold, or with a free-breathing CT scan. The ITV can be developed as an expansion margin on the CTV based on motion assessment on 4D-CT scan or as a separate volume that encompasses the CTV target area on all 10 phases of the 4D-CT or on the MIP image (maximum intensity projection). In the latter case, an ITV would be generated without a CTV. A patient undergoing breath hold may not have an ITV; however, if multiple breath holds are done at the time of simulation, a CTV incorporating coverage on all breath hold scans would also be considered an ITV. In cases involving proton therapy, it is essential to delineate a CTV or ITV as part of the targeting process.

4. Planning Target Volume (PTV)

The PTV is defined as the CTV or ITV with a geometric margin. The PTV should encompass the CTV and ITV, and accounts for geometric variation in daily setup. It should take into account the reproducibility of the immobilization, and the accuracy of the daily setup imaging. In general, PTV expansion of 5–10 mm should be made on a CTV or ITV.

Discussion and Conclusion

PD-RT utilizes post-treatment PET imaging to target areas of highest risk of relapse, and consists of pISRT, pRSRT and pRPRT. PD-RT is being used on contemporary lymphoma clinical trials, alone or as a boost in combination with ISRT. There is no standardized nomenclature for PD-RT volumes which makes its adoption and robustness challenging. The NCTN forum of lymphoma radiation oncologists is proposing a consensus nomenclature for the contemporary PD-RT target volumes being used on recent and current NCTN lymphoma clinical trials. The goal of this consensus approach is to reduce ambiguity and promote standardized adoption of these nomenclatures in future clinical trials. It is important to note that although a considerable number of these studies enrolled advanced-stage patients, for whom smaller PD-RT fields might be reasonable to employ, ISRT remains the standard of care for limited stage disease. Recommendations for using these target volumes are beyond the scope of this work.