Hodgkin Lymphoma Flashcards by Mario Luna

Hodgkin Lymphoma

What are the two peaks (age range) when there is increased incidence of HL (5.5 per 100,000)?

25 to 30

75 to 80

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Hodgkin Lymphoma

It is the most common malignancy diagnosed among patients 15 to 19 years olds.

TRUE or FALSE?

True

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Hodgkin Lymphoma

This disease has an equal male-female distribution,

TRUE or FALSE?

False

Male predominance (1.2 : 1)

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Hodgkin Lymphoma

What virus has been proposed to have a relationship with the development of HL?

(This is also proposed as related to the development of the MCHL subtype in children in developing countries)

EBV

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Hodgkin Lymphoma

What are the usual clinical presentations of HL?

painless adenopathy
incidental mediastinal mass on routine chest radiograph
systemic symptoms (unexplained fevers, drenching night sweats, weight loss, generalized pruritus, fatigue, and alcohol-induced pain in tissues involved by HL)

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Hodgkin Lymphoma

Majority of involved sites are contiguous.

TRUE or FALSE?

True

Sites of involvement are typically contiguous, although occasional skip areas
occur.

The theory of contiguity of spread and the development of treatment
programs with radiation that included treatment of uninvolved sites were
important conceptual advances in the treatment of HL in the latter half of the
20th century.

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Hodgkin Lymphoma

Explain the pathophysiology of the classic finding of ivory vertebra on plain radiographs

they are blastic changes on the bones due to hematogenous seeding

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Hodgkin Lymphoma

Enumerate some laboratory findings that are considered adverse prognostic factors especially in advanced disease.

anemia
lymphopenia
leukocytosis
hypoalbuminemia

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Hodgkin Lymphoma

Define “bulky” mediastinal adenopathy
3 ways

> 1:3 ratio to the maximum intrathoracic diameter (near the level of the diaphragm) on standing PA radiograph

> 10 cm

ratio >0.34 at the level of T5-T6 (EORTC)

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Hodgkin Lymphoma

Definition of an enlarged cervical lymph node on contrast-enhanced CT?

> 1.5 cm

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Hodgkin Lymphoma

In the absence of confirmatory findings of HL involvement in the spleen, a spleen of this size is considered likely involved per the current staging system.

> 13-cm long

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Hodgkin Lymphoma

FDG’s uptake pattern in bone defines whether bone or bone marrow is involved, obviating the need for a bone marrow biopsy.

TRUE or FALSE?

True

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Hodgkin Lymphoma

Specify the Deauville score:

No uptake

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Hodgkin Lymphoma

Specify the Deauville score:

New areas of uptake unlikely to be related to lymphoma

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Hodgkin Lymphoma

Specify the Deauville score:

Uptake moderately higher than liver

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Hodgkin Lymphoma

Specify the Deauville score:

Uptake markedly higher than liver

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Hodgkin Lymphoma

Specify the Deauville score:

New lesions

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Hodgkin Lymphoma

Specify the Deauville score:

Uptake > mediastinum but ≤ liver

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Hodgkin Lymphoma

Specify the Deauville score:

Uptake ≤ mediastinum

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Hodgkin Lymphoma

Specify the Ann Arbor Stage:

Involvement of a single lymph node region

stage I

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Hodgkin Lymphoma

Specify the Ann Arbor Stage:

Involvement of a single lymph node region and a localized extralymphatic organ on the same side of the diaphragm.

stage IIE

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Hodgkin Lymphoma

Specify the Ann Arbor Stage:

Involvement of a single lymph node region with and an a diffuse extralymphatic organ on the same side of the diaphragm.

stage IV

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Hodgkin Lymphoma

Specify the Ann Arbor Stage:

No lymph node involvement
Diffuse involvement of an extralymphatic organ on the same side of the diaphragm.

stage IV

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Hodgkin Lymphoma

Specify the Ann Arbor Stage:

Involvement of 2 or more lymph node regions on the same side of the diaphragm.

Stage II

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Hodgkin Lymphoma Specify the Ann Arbor Stage: Involvement of two lymph node regions on both sides of the diaphragm

III

Hodgkin Lymphoma This system used X to designate bulky disease starting in 1989

Cotswolds modification of the Ann Arbor

Hodgkin Lymphoma This system recommended deleting X to designate bulky disease starting in 2014 and instead note the size of the largest node

Lugano modification of the Ann Arbor

Hodgkin Lymphoma What are two major categories of HL as defined by the WHO?

classic and nodular lymphocyte–predominant HL (NLPHL)

Hodgkin Lymphoma Describe the morphology R-S cell, the signature neoplastic cell of HL.

- binucleate - prominent nucleolus in each nucleus - well-demarcated nuclear membrane - perinuclear halo - eosinophilic cytoplasm

Hodgkin Lymphoma Describe the immunohistochemical staining results of R-S cell, the signature neoplastic cell of HL.

Positive for: CD30/lymphocyte activation marker PAX5 (dimly) CD20 (variably) CD15/antigranulocyte monoclonal antibody (variably) express PD-1/PDL-1 ligand Negative for: CD45 ALK J Chain

Hodgkin Lymphoma Enumerate the 4 subtypes of HL.

NSHL MCHL LRHL LDHL

Hodgkin Lymphoma This is characterized by lymph nodes that are diffusely effaced by lymphocytes, eosinophils, plasma cells, inflammatory cells, and relatively abundant atypical mononuclear and R-S cells.

MCHL

Hodgkin Lymphoma What is the most common histologic subtype diagnosed in developed countries?

NSHL

Hodgkin Lymphoma It is characterized by involved nodes that often have a thick capsule and are traversed by broad bands of birefringent collagen that surround nodules of cells consisting of lymphocytes, eosinophils, plasma cells, and tissue histiocytes intermixed with a variable proportion of atypical mononuclear cells, inflammatory cells, and R-S cells

NSHL

Hodgkin Lymphoma Identify the classical HL subtype: Patients are usually young women, with a favorable natural history and typically present in the clinic with mediastinal involvement, and one-third have B symptoms.

NSHL

Hodgkin Lymphoma Identify the classical HL subtype: Patients usually present with advanced disease and tend to be slightly older and have a less favorable natural history than those with NSHL.

MCHL

Hodgkin Lymphoma Identify the classical HL subtype: It is difficult to differentiate this subtype from anaplastic large cell lymphoma especially because both are CD30+.

LDHL

Hodgkin Lymphoma Identify the classical HL subtype: It is the most uncommon, and has the worst prognosis of the four subtypes.

LDHL

Hodgkin Lymphoma Identify the classical HL subtype: This is confused with LPHL due to the clinical characteristics: early stage, absence of B symptoms, and excellent prognosis. However, the staining characteristic is that of classical HL.

LRHL

Hodgkin Lymphoma Describe the staining characteristics of the L&H cells/popcorn cells of the NLPHL.

``` strongly positive for: CD20 CD45 CD79a PAX5 ``` negative for: CD15 CD30

Hodgkin Lymphoma What is the most common presenting profile of patients with NLPHL?

young people who present with early-stage disease, usually in a solitary peripheral nodal site. Systemic symptoms are uncommon

Hodgkin Lymphoma Identify the values that would make a patient with advanced HL to have "unfavorable" prognosis based on the International Prognostic Scoring System Serum albumin

<4 g/dL

Hodgkin Lymphoma Identify the values that would make a patient with advanced HL to have "unfavorable" prognosis based on the International Prognostic Scoring System Hemoglobin

<10.5 g/dL

Hodgkin Lymphoma Identify the values that would make a patient with advanced HL to have "unfavorable" prognosis based on the International Prognostic Scoring System Gender

Male

Hodgkin Lymphoma Identify the values that would make a patient with advanced HL to have "unfavorable" prognosis based on the International Prognostic Scoring System Age

≥45 y

Hodgkin Lymphoma Identify the values that would make a patient with advanced HL to have "unfavorable" prognosis based on the International Prognostic Scoring System Ann Arbor Stage

Hodgkin Lymphoma Identify the values that would make a patient with advanced HL to have "unfavorable" prognosis based on the International Prognostic Scoring System Leukocyte count

>15,000/mm3

Hodgkin Lymphoma Identify the values that would make a patient with advanced HL to have "unfavorable" prognosis based on the International Prognostic Scoring System Lymphocyte count

<8% of WBC or <600/mm3

Hodgkin Lymphoma Chemotherapy. What agents are included in ABVD?

doxorubicin bleomycin vinblastine dacarbazine

Hodgkin Lymphoma Chemotherapy. What agents are included in BEACOPP?

``` bleomycin etoposide doxorubicin cyclophosphamide vincristine prednisone procarbazine ```

Hodgkin Lymphoma Chemotherapy. What agents are included in Stanford V

``` bleomycin doxorubicin vinblastine vincristine etoposide prednisone nitrogen mustard ``` (BEAVOPe) + nitrogen mustard

Hodgkin Lymphoma Targeted therapy. This is an anti CD30 linked to an antitubulin which has demonstrated efficacy in CD30+ lymphomas. This has also been approved as a maintenance therapy following autologous HCT (ETHERA trial).

BV brentuximab vedotin

Hodgkin Lymphoma Targeted therapy. This is checkpoint inhibitor approved for patients with disease that is chemoresistant or has relapsed after 3 or more lines of therapy.

Pembrolizumab

Hodgkin Lymphoma Targeted therapy. This checkpoint inhibitor has been approved or patients whose disease has relapsed or progressed after autologous HCT and posttransplant brentuximab

Nivolumab

Hodgkin Lymphoma What is the ISRT treatment field recommended for "early" stage "favorable" disease that was treated with "abbreviated" chemotherapy?

ISRT all initial sites of disease after completing chemotherapy

Hodgkin Lymphoma What is the ISRT treatment field recommended for NLPHL disease that will be treated with RT alone?

ISRT CTV all initial sites + potenital subclinical disease (2- to 5-m margin within the lymphatic stations superior and inferior to the initially involved disease)

Hodgkin Lymphoma What is the ISRT treatment field recommended for "early" stage "unfavorable" disease that was treated with "abbreviated" chemotherapy?

ISRT to all sites of disease

Hodgkin Lymphoma What is the ISRT treatment field recommended for "early" stage "unfavorable" disease that was treated with "intensive" chemotherapy?

ISRT certain complete responding areas that could result in unacceptable OAR doses can be omitted

Hodgkin Lymphoma What is the ISRT treatment field recommended for "advanced" stage disease?

ISRT to sites of initially bulky disease or sites of incomplete response it is presumed that the patient was treated with intensive chemotherapy because of the advanced stage.

Hodgkin Lymphoma For patients with initially large mediastinal masses, what is the postchemotherapy CTV?

the width should conform to the residual disease only, | the superior and inferior border should encompass the initial extent of disease.

Hodgkin Lymphoma What is the NCCN recommended dose for RT alone?

30 to 36 Gy to involved sites 25 to 30 Gy to potential subclinical involvement 1.5- to 2.0-Gy per fraction

Hodgkin Lymphoma What is the NCCN recommended RT dose for RT as a component of combined modality treatment?

30 to 36 Gy to involved sites 1.5- to 2.0-Gy per fraction Deauville 4-5 lesions may be treated from 36 to 45 Gy.

Hodgkin Lymphoma OARs What are the doses at which there is an increased risk for RTOG grade 2 pneumonitis?

mean lung dose >14 Gy | V20 >35%

Hodgkin Lymphoma OARs What are the threshold doses for RTOG grades 1-3 pneumonitis? (doses should be keep below this)

mean lung dose 13.5 Gy V20 <30 V5 <55

Hodgkin Lymphoma OARs The risk of radiation-related pneumonitis s also increased with the use of what chemotherapy or targeted agent/s that also cause significant pulmonary toxicities.

bleomycin and BV (they should be never used simultaneously) nivolumab and pembrolizumab as well.

Hodgkin Lymphoma OARs What is the threshold dose for the development of secondary lung cancer?

5 Gy

Hodgkin Lymphoma OARs What is the threshold dose for the development of secondary breast cancer?

4 Gy

Hodgkin Lymphoma OARs What is the relationship of coronary heart disease and mean heart dose?

the excess relative risk (ERR) was 7.4% per Gy of MHD. The ERR was negligible with an MHD <5 Gy and was approximately 2 for an MHD of 12 Gy

Hodgkin Lymphoma OARs At what dose is there an increased ERR for valvular diseases?

>20 Gy

Hodgkin Lymphoma OARs At what dose is there an increased risk for congesitve heart failure?

left ventricular mean dose exceeds 15 Gy, or V30 is ≥50%

Hodgkin Lymphoma OARs At what dose to the pericardium is there an increased risk for pericarditis?

>30 Gy esp if using mantle field

Hodgkin Lymphoma Unfavorable disease characteristics of early stage I to II HL EORTC

age ≥50 ESR ≥30 with any B sx ESR ≥50 without B sx Mediastinal mass MTR ≥0.35 (T5-6 level) >3 nodal regions

Hodgkin Lymphoma Unfavorable disease characteristics of early stage I to II HL GHSG

ESR (similar to EORTC) ESR ≥30 with any B sx ESR ≥50 without B sx MMR > 0.33 >2 nodal regions Any extralymphatic involvement

Hodgkin Lymphoma Unfavorable disease characteristics of early stage I to II HL NCIC

Age ≥40 MC/LD histology ESR ≥50 OR any B sx MMR > 0.33 >3 nodal regions

Hodgkin Lymphoma Unfavorable disease characteristics of early stage I to II HL NCCN

Any B sx ESR >50 mm 10 cm mass or MMR > 0.33 >3 nodal regions

Hodgkin Lymphoma What is the treatment for early stage favorable HL with only 1 or 2 disease sites, <50 EST, no extranodal disease?

2 cycles of ABVD + 20 Gy ISRT | GHSG

Hodgkin Lymphoma What is the standard treatment for early stage favorable HL? No interim PET was done.

CMT 4 cycles of ABVD + 30 Gy ISRT

Hodgkin Lymphoma What is the standard treatment for early stage favorable HL? Consider a negative interim PET CT (Deauville 1 or 2).

CMT 3 cycles of ABVD (or 8 weeks of Stanford V) + 30 Gy ISRT

Hodgkin Lymphoma What is the standard treatment for early stage favorable HL? Consider a positive interim PET CT after 2 cycles of ABVD but no progressive disease

additional 2 cycles of ABVD + 30 Gy ISRT or 2 cycles of escalated BEACOPP + 30 Gy ISRT.

Hodgkin Lymphoma Can early-stage favorable HL be treated with ABVD alone?

yes. (NCIC-CTG HD.6 trial). 12 years 94% survival rate 87% PFS.

Hodgkin Lymphoma What is the CTV expansion for ISRT in NLPHL (Stage I to IIA)

The CTV expansion must account for possible microscopic spread beyond the lymph nodes clinically observed on PET-CT imaging. For a patient who presents with unilateral level I or IIA disease, the CTV should be expanded to include ipsilateral levels IIB, III, and even IV. For a femoral node presentation, the CTV should include at least a 5-cm extension along the lymphatic chains superiorly and a 2-cm extension inferiorly

Hodgkin Lymphoma Based on ESMO and NCCN guidelines, what are the treatment recommendations for stage I and limited stage II respectively?

RT alone for stage I CMT for stage II, unless it is non bulky with no more than 2 contiguous sites involved.

Hodgkin Lymphoma What is the standard treatment most commonly used for stage I or II HL with large mediastinal adenopathy?

4-6 ABVD + 30 Gy ISRT. (However, EORTC H9U showed no significant benefit to 6 cycles vs 4 when given with RT).

Hodgkin Lymphoma What is the IFRT dose if BEACOPP is used for patients with intermediate prognosis?

20 Gy IFRT. | However, BEACOPP is more toxic than ABVD hence, 4 ABVD + 30 Gy IFRT can be considered.

Hodgkin Lymphoma Can you omit RT for stage III to IV HL? When?

Yes. If there is CR to a full course of conventional chemotherapy. However, RT is often added for patients with bulky disease or suspected residual sites.

Hodgkin Lymphoma What is the dose for RT given prior to HCT?

similar to TBI (12 to 15 Gy)

Hodgkin Lymphoma If the RT will be given after HCT, when do you do it and what are your targets?

1 to 4 months after. to sites of bulky disease at the time of relapse or sites that remain positive on PET before transplant. You may also include all sites involved at the time of relapse.

Hodgkin Lymphoma What is the dose for RT given after HCT?

18 to 40 Gy In general, lower doses were employed when initially nonbulky disease was included in the treatment or when there was a CR to high-dose therapy.

Hodgkin Lymphoma Follow-up schedule during the first 2 years following treatment.

every 3 to 6 months

Hodgkin Lymphoma Follow-up schedule after 2 years following treatment.

every 6 to 12 months

Hodgkin Lymphoma Identify: This develops in approximately 10% to 15% of patients after radiation therapy to a significant length of the spinal cord via AP/PA fields. It is more likely to occur among patients who have been treated with vinca alkaloids (vincristine and vinblastine).

Lhermitte sign

Hodgkin Lymphoma An uncommon but potentially serious complication is overwhelming sepsis after splenectomy or splenic irradiation. What are the most common organisms involved?

Streptococcus pneumoniae Hemophilus influenzae type b Neisseria meningitidis

Hodgkin Lymphoma What chemotherapy regimen is considered safe to avoid male infertility following HL treatment?

ABVD and Stanford V | MOPP and BEACOPP can cause sterility

Hodgkin Lymphoma What chemotherapy regimen is considered safe to avoid female infertility following HL treatment?

ABVD and Stanford V | MOPP and BEACOPP can cause sterility

Hodgkin Lymphoma What secondary lymphoma is most common after treatment of HL?

DLBC

Hodgkin Lymphoma What disease has a potential risk of developing if a large portion of the pericardium is treated, which is uncommon in the current management programs; it presents as an acute febrile syndrome associated with chest pain and friction rub, an asymptomatic pericardial effusion diagnosed by chest radiograph or echocardiogram, or constrictive pericarditis or tamponade. Mild manifestations can be managed with conservative medical treatment including analgesics and nonsteroidal antiinflammatory agents; it usually clears within a few weeks.

Radiation pericarditis

Hodgkin Lymphoma Flashcards

(96 cards)