Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2915_Библиотеки_им_академика_М_И_Перельмана.pdf
Non-Hodgkin’s Lymphoma
211
Figure 3.
As lymphomas occur at several anatomical sites, the scan should include the whole
volume of critical organs such as lung, liver, and kidneys for DVH assessment. Traditionally,
wide or extended field radiotherapy treatments called as ‘Mantle’ and ‘Inverted Y’ were used
as primary treatment for lymphomas with satisfactory cure rates but with a high rate of late
toxicity, mainly, to the heart, lungs and breasts (figure-4).
Figure 4. Mantle field design for radiotherapy treatment.
With multimodality treatment combining chemotherapy and adjuvant radiotherapy,
evidences have supported the use of local radiotherapy instead of extended fields, to reduce
toxicity. There are three possible approaches to using smaller volume treatments. Since
lymphatic spread involves nodes adjacent to the primary site of disease first, locoregional
treatment that includes elective adjuvant irradiation of the first node stations may be given
(IFRT). The CTV includes the GTV, which is the primary site, and adjacent nodes as CTV (a
Gustavo Arruda Viani
212
situation analogous to treatment of uninvolved nodes in head and neck cancer). Alternatively,
only the initial macroscopic volume of disease (GTV), whether in lymph node (involved
nodal INRT), or an organ (sometimes called involved site ISRT) is treated with a GTV-CTV
margin. Finally, the residual GTV following chemotherapy, defined by PET-CT, could be the
basis of the target volume. In published reports the target volumes used may combine aspects
of these different conceptual approaches. When primary radiotherapy without chemotherapy
is given (e.g. stage I follicular non-Hodgkin’s lymphoma or nodular lymphocyte predominant
Hodgkin’s lymphoma), IFRT is used to include the uninvolved first node station in the CTV
as well as the macroscopically involved GTV. The CTV is designed using the initial volume
of involved lymph nodes, i.e. the initial GTV as shown on staging CT, MRI and FDG-PETCT scans. These scans need to be taken in the radiotherapy treatment position, whenever
possible, for accurate co-registration with subsequent CT planning scans which are taken after
chemotherapy. When primary radiotherapy is given, the GTV is present both clinically and on
imaging. After chemotherapy there may be a complete response (PET and CT negative) with
no GTV, or a partial response with a residual GTV. The original GTV is outlined on the postchemotherapy CT planning scan using the co-registered initial CT and PET scans. The
patient’s anatomy will have altered with response to chemotherapy, and the principle is to
cover the site of original disease, but to reduce toxicity by excluding wherever possible
normal tissues that were displaced, but not involved by tumour. Anatomical planes act as
boundaries and the volume should not extend into adjacent bone, air or viscera. For both
IFRT and INRT of the mediastinum, the pre-chemotherapy volume is used for the superior–
inferior extension and the post-chemotherapy volume for the axial to reduce dose to blood
vessels, heart, coronary arteries and lung which may have returned to their normal position
(Figure-5).
Figure 5. Evolution of radiotherapy fields.
Where there was definite tumour infiltration into adjacent tissues at diagnosis, the whole
volume should still be included. The CTV for IFRT includes the clinically and radiologically
involved lymph nodes as imaged at presentation (GTV) with the adjacent lymphatics and
uninvolved first node station. Radiation doses between 36 - 40 Gy delivered in conventional
fractionation is recommended for the treatment of low-grade NHL with curative intent, and a
dose higher than 40 Gy may be required for bulky disease. Lowgrade lymphomas are
generally radio-responsive diseases. Total lymphatic irradiation (TLI) can be recommended
for a selected group of patients with stage III indolent NHL. Patients with fewer than five
Non-Hodgkin’s Lymphoma
213
sites of disease involvement (nonbulky) and no signs of “B” symptoms may benefit from total
lymphatic irradiation. The radiation portal of TLI should encompass cervical, supraclavicular,
axillary, mediastinal, paraaortic, mesenteric, pelvic, and femoral lymphatics (figure-6).
Figure 6.Total nodal irradiation fields.
Conclusion
• NHL is a heterogeneous group of malignancies which has historically been classified
a variety of ways.
• Actually, the classification system take into account the cells of origin for NHL. The
clinically relevant classification schemes separate the diseases into indolent and
aggressive NHL.
• Treatment of NHL depends on the clinical classification of the tumor (indolent
versus aggressive) and the stage.
• Radiotherapy plays an important role in the treatment of limited-stage indolent and
aggressive lymphomas, and may be of benefit for select patients with advanced-stage
aggressive NHL.
Chapter 14
Hodgkin’s Lymphoma
Abstract
In the U.S.A occur approximately 8000 new cases per year. North America and
Western Europe with highest incidence. Black and Asian populations with lower
incidence.
Unknown but aberrant B-cell response to antigen in susceptible individuals
suggested.
Relationship to Epstein-Barr virus (EBV) in a subset by unknown mechanism.
Genetic component suggested by increased risk in families.
Classical Hodgkin's lymphoma (HL) diagnosed by CD15+ CD30+ Reed-Sternberg
cells within a characteristic inflammatory background.
Nodular lymphocyte predominance HL diagnosed by CD20+ CD15- CD30- L&H
cells with characteristic architecture and background.
Lymphadenopathy, mainly supradiaphragmatic sites. Mediastinal adenopathy
causing chest symptoms. “B” symptoms: night sweats, fevers, weight loss.
History, physical examination, complete blood count, serum chemistry, ESR.
Image studies: computed tomography of chest, abdomen and pelvis; whole body
positron emission tomography.
Patients with B symptoms and/or advanced disease should have bone marrow
biopsy.
Early stage: chemotherapy and involved field radiotherapy;
Advanced stage: multiagent chemotherapy for six to eight cycles with ABVD
(doxorubicin, bleomycin, vinblastine, doxorubicin) or BEACOPP (bleomycin,
etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone)
with or without radiotherapy.
Cure achieved in more than 90% of patients with favorable, early stage disease.
Advanced disease cured in 60% to 85% of patients, dependent on clinical prognostic
score and age.
Introduction
Hodgkin’s lymphoma is a highly curable disease with distinct histology, biologic
behavior, and clinical characteristics. Thomas Hodgkin first described the disorder in 1832.
Gustavo Arruda Viani
216
Familiar history
First-degree relatives of patients have fivefold increase in risk for Hodgkin’s
disease.
Infection
Associated with Epstein–Barr virus, which is associated with Mixed cellularity
subtype.
EBV DNA has been detected in Reed- Sternberg cells.
Associated with HIV infection.
Social factors
The first peak of HL is associated with a higher social class, advanced
education, and small family size.
The disease is defined in terms of its microscopic appearance and the expression of cell
surface markers. Treatment for Hodgkin’s lymphoma is based on multiagent chemotherapy,
with or without radiation therapy. In this chapter we will discuss all aspects on the role of
radiotherapy in treatment HL.
1. Epidemiology
• Hodgkin’s lymphoma (HL) is histologically characterized by the presence of various
numbers of multinucleated giant cells (Reed–Sternberg cells) within a mixed
inflammatory infiltrate, and it originates from the lymphoid system.
• HL was firstly defined by Thomas Hodgkin in 1832. HL accounts for about 1% of
new cancer cases annually in the United States, or 7,000 cases per year.
• The incidence of HL has remained stable over the last two to three decades and is
bimodal, with the first peak in the third decade in life, and a second, smaller peak
after 50 years of age.
• The first peak, constituting predominantly the nodular sclerosis subtype, occurs in
the 20s and the second peak occurs after 50 years of age.
• In third-world countries, the first peak is absent, but there is a significant incidence of
mixed cellularity and lymphocyte-depleted HL in men.
• The nodular sclerosing subtype of HL shows a slight female predominance, whereas
the other histologic subtypes are more common in men.
References
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10.
2. Risk Factors
The etiology of HL is unknown, but, there are a limited number of factors documented.
The table-1 describes the main factors.
Table 1. risk factors associated with HL
Hodgkin’s Lymphoma
217
Reference
Alexander FE, Jarrett RF, Lawrence D et al. Risk factors for Hodgkin's disease by Epstein-
Barr virus (EBV) status: prior infection by EBV and other agents. Br J Cancer.
2000;82(5):1117.
3. Anatomy
Lymph node regions were described for by Kaplan et al with staging purposes and have
been in use for over 40 years
Figure 1. Kaplan regions for lymph node regions.
Reference
Kaplan H, Rosenberg S (1966) The treatment of Hodgkin’s disease. Med Clin North Am
50:1591–1610, Copyright 1996, Elsevier
Gustavo Arruda Viani
218
4. Clinical Features
• HL almost always originates in a lymph node. Painless lymphadenopathy of growing
slow is a common symptom.
• The most common site for HL is the cervical region (80%). Axilla and inguinal
region involvement is rare. Mediastinal mass is common, occurring in 80% of cases,
and when the disease is bulky, might cause symptoms (chest pain, cough, and
dyspnea). Hepatosplenomegaly is rare.
• Whenever a primary diagnosis of HL is made in an extranodal site without
contiguous nodal involvement, the diagnosis should be highly suspect.
• HL appears to spread in an orderly fashion through the lymphatic system by
contiguity.
• Histologic types other than NS, however, often skip the mediastinum, and disease
appears in the neck and upper abdomen. The axial lymphatic system is almost always
affected in HL, whereas distal sites (e.g., epitrochlear and popliteal nodes) are rarely
involved.
• Hematogenous dissemination occurs late in the course of disease and is characteristic
of the LD subtype.
• In addition, itching and pain after alcohol intake may be observed. B symptoms of
night sweats, fever, and weight loss are reported in approximately 30% of patients.
• Splenic involvement is seen in nearly all cases with bone marrow and hepatic
involvement. Other less frequent symptoms include pruritus and alcohol- induced
pain localized over the involved lymph node.
References
Swerdlow SH, Campo E, Harris NL, et al. (Eds). World Health Organization Classification of
Tumours of Haematopoietic and Lymphoid Tissues, IARC Press, Lyon 2008.
Mauch PM, Kalish LA, Kadin M, Coleman CN, Osteen R, Hellman S. Patterns of
presentation of Hodgkin’s disease. Implications for etiology and pathogenesis. Cancer.
1993;71(6):2062.
5. Pathology
The Rye classification for HL relates the histopathologic subtypes to clinical behavior
and prognosis. This older classification system comprises lymphocyte-predominant (LP),
nodular sclerosing (NS), mixed-cellularity (MC), and the uncommon lymphocyte-depleted
(LD) varieties of HL. The LP subtype was further divided into nodular LP and diffuse LP
subtypes. Immunohistochemistry, however, has resulted in deletion of the diffuse LP subtype
and redefinition of the nodular LP subtype (table-2).
Hodgkin’s Lymphoma
219
Histology
Description
Nodular lymphocyte
predominant HL (2–
5%)
Accounts for <5% of HL, usually presents in middle-aged males, with
localized peripheral lymph node involvement (cervical, axillary, and inguinal
regions).
Nodular sclerosing HL
(~65%)
The most common subtype of HL, accounting for 65–70%
of cases, and is the only subtype without a male predominance (male:female
ratio approximately 1:1)
Lymphocyte-rich HL
(~10%)
Similar to nodular sclerosing clinically, with localized disease at presentation
involving a peripheral lymph node region
Mixed cellular HL
(~20%)
Commonly presenting in advanced stages, with a tendency
to involve spleen, bone marrow, and a lesser tendency
for mediastinal involvement
Lymphocyte-depleted
HL (<5%)
Very rarely seen in primary presentation, as many of the
previous cases were probably misdiagnosed, and have
now been recognized as the worse prognosis among the HL subtypes
Table 2. Histological subtypes for HL
Reference
Swerdlow SH, Campo E, Harris NL, et al. (Eds). World Health Organization Classification of
Tumours of Haematopoietic and Lymphoid Tissues, IARC Press, Lyon 2008.
6. Diagnostic and Evaluation
• Evaluation of HL begins with a complete history and physical examination with
special attention to disease related signs and symptoms.
• Fever of 38C or higher for 3 consecutive days, drenching night sweats, and
unexplained weight loss >10% over 6 months prior to diagnosis (the “B” symptoms)
should be evaluated. Patients presenting with fever and weight loss have a worse
prognosis. Pel- Ebstein fever is the classical descriptor for the waxing and waning
fever of HL.
• Other commonly observed symptoms of HL include pruritus, painless lymphadeno-
pathy, respiratory difficulty, alcohol-induced pain, and fatigue. Thorough examination of all lymphoid regions including the spleen and the liver is required. In total
80% of patients present with cervical lymphadenopathy, while 50% present with
mediastinal lymphadenopathy. Involvement of Waldeyer’s ring or mesenteric lymph
nodes is rare (<5%).
• HL spreads in an orderly, contiguous pattern through lymph nodes. As the disease
advances, hematogenous metastasis may occur to liver and bone.
• Adequate surgical biopsy reviewed by experienced hematopathologist is necessary to
establish the diagnosis. Fine-needle aspiration is not an adequate means of initial
diagnosis. Laboratory tests should include: CBC with differential and platelet count,
serum chemistries including LDH, ESR, urinalysis.
• A CT scan of the neck, chest, abdomen, and pelvis with contrast should be
performed.
Gustavo Arruda Viani
220
• Bone marrow aspiration and biopsy (bilateral iliac crest) is required for advanced
stage, unless clinical stage IA to IIA with no anemia or other blood count depression.
• Bone scan in presence of bone pain, or elevated serum alkaline phosphatase or
calcium level.
• PET scans are optional but are useful in follow-up of residual masses on chest
radiograph or CT scan after therapy, given the propensity of treated HL nodes to
remain visible on CT scans (figure-2).
• HIV testing should be considered in patients whose disease presentation is primarily
extranodal.
• Pregnancy test and fertility counseling in patients of childbearing age should be
performed with staging evaluation.
Figure 2. CT scan and PET CT of patients with mediastinal lymph node involvement.
References
Castellino RA, Hoppe RT, Blank N, Young SW, Neumann C, Rosenberg SA, Kaplan HS.
Computed tomography, lymphography, and staging laparotomy: correlations in initial
staging of Hodgkin’s disease. AJR Am J Roentgenol. 1984;143(1):37.
Naumann R, Beuthien-Baumann B, Reiss A et al. Substantial impact of FDG PET imaging on
the therapy decision in patients with early-stage Hodgkin's lymphoma. Br J Cancer.
2004;90(3):620.
Vassilakopoulos TP, Angelopoulou MK, Constantinou N et al. Development and validation
of a clinical prediction rule for bone marrow involvement in patients with Hodgkin’s
lymphoma. Blood. 2005;105(5):1875.
7. Staging
The Ann Arbor Staging System had previously been universally used but has been
modified to take into account important prognostic factors, particularly mediastinal bulk
(table- 3).