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1618 Part XI: Malignant Lymphoid Diseases Chapter 97: Hodgkin Lymphoma 1619

adolescents. 152,244–246 Case-control studies have examined the relation- risk should be monitored during followup observation. Rarely, hyper-
ship of radiation dose to the breast and the risk of cancer, finding a thyroidism, Graves ophthalmopathy or thyroid neoplasms occur after
3.2-fold increased risk with doses greater than 4 Gy and an eightfold neck radiotherapy. Lhermitte sign, a transient complaint of an “elec-
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risk for doses greater than 40 Gy. 247,248 Elimination of routine axillary tric shock” sensation produced by head flexion, is a common sequela
270
radiation, which is now standard, results in a 2.7-fold reduction in risk of mantle radiotherapy. The incidence of radiation pneumonitis
and it is anticipated that risks may further decline with current low-dose depends on the volume of lung irradiated and the total dose. Symptoms
or nodal radiotherapy. Cofactors are important for defining the risks of include cough, dyspnea, and fever. Although prospective assessment of
second breast cancer, which are highest for women younger than age pulmonary function demonstrates reduction of lung volumes following
30 years when irradiated and for those who continue to have normal mantle radiotherapy, recovery is seen in 12 to 24 months and symptom-
menses. 249,250 atic radiation pneumonitis is unusual. 271,272
Lung cancer risk is greatest among patients who are older than Full-dose radiation therapy interferes with normal growth and
45 years of age when treated. Tobacco exposure has a multiplying effect development in children. Current therapy programs use low-dose
and alkylating agent exposure also contributes to risk. Among patients or no radiotherapy for all stages of disease. Overwhelming sepsis is a
with chest irradiation, a tobacco history, and alkylating chemotherapy, rare event in patients who have been splenectomized and treated for
the lung cancer risk was 49-fold higher than in patients who had none Hodgkin lymphoma, particularly children. 273,274 Vaccination against
of these exposures. Alkylating agent chemotherapy independently encapsulated organisms 10 to 14 days prior to the onset of treatment
248
increases risk of lung cancer with dose–response associations reported is advised. However, it must be recognized that neither vaccines nor
in population-based studies. 247,248,251 antibiotic prophylaxis may provide adequate protection. Fatigue is com-
Estimates of relative risks of cardiac mortality in Hodgkin lym- monly reported in Hodgkin lymphoma survivors and has been related
phoma survivors range from 2.2- to sevenfold. 233,234,252,253 Mediastinal to pulmonary function and peak oxygen uptake. 255,275
radiotherapy is associated with an increased risk of cardiac disease. An With the high rates of cure currently attained in the management
increased risk of death from coronary artery disease and acute myocar- of Hodgkin lymphoma, reduction in late effects and quality of life
dial infarction has been identified in adults and children. 245,253,254 Other assume even greater importance. Patient education is essential to pro-
types of cardiac disease are often asymptomatic, including valvular mote healthy behaviors to reduce modifiable risk factors. In addition,
disease, conduction defects, and cardiomyopathy. 255,256 The risks of early detection and prevention strategies for second cancers and car-
radiation-related heart disease do not appear to be influenced signifi- diac disease should be considered in high-risk patients. However, the
cantly by the addition of chemotherapy. The onset of increased risk is choice and efficacy of diagnostic testing, and their optimal timing and
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within 5 to 10 years. As risk is associated with the dose and volume of frequency, require further study. Most of the documented late effects
radiotherapy and the latency is 5 to 10 or more years, the hazards associ- relate to outdated chemotherapy and radiotherapy protocols, and that
252
ated with current lower dose and smaller fields remain to be assessed. modeling, as well as recent data, indicate that lesser exposures signifi-
Established cardiac risk factors, including hypertension, hypercholester- cantly reduce second cancer risk. 249,277 Modern therapies will likely fur-
olemia, and smoking, significantly contribute to the subsequent risk of ther reduce the risks of late complications. It continues to be important
cardiac disease after therapy, offering opportunities to reduce individual to follow long-term survivors, and the contribution of genetic and envi-
risks. A British report indicated an elevated risk of cardiac mortality ronmental factors is an important ongoing area of inquiry.
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of 7.8-fold following ABVD alone, which rose to 12.1-fold when given
with mediastinal irradiation. These results provide a cautionary note, REFERENCES
258
but more data are needed and these results do not address cumulative
exposures that are lower with modern therapy. 1. Hodgkin T: On some morbid appearances of the absorbent glands and spleen. Med Chir
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cohort study, the standardized incidence ratio for was 2.2 for stroke and 4. Kundrat H: Uber Lympho-Sarkomatosis. Wien Klin Wochenschr 6:211–234, 1893.
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3.1 for transient ischemic attack. However, it is important to note that 5. Sternberg C: Über eine eigenartige unter dem Bilde der Pseudoleukämie verlaufende
Tuberculose des lymphatischen Apparates. Ztschr Heilk 19:21–90, 1898.
modern approaches to Hodgkin lymphoma therapy use lower radiation 6. Reed D: On the pathological changes in Hodgkin’s disease, with special reference to its
doses, smaller fields, and planning techniques that limit dose inhomoge- relation to tuberculosis. Johns Hopkins’ Hosp Rep 10:133–196, 1902.
neity and hot spots commonly seen in the neck area with older techniques. 7. Fox H: Remarks on microscopical preparations made from some of the original tissue
described by Thomas Hodgkin, 1832. Ann Med Hist 8:370–374, 1926.
Approximately 90 percent of males are permanently sterilized by 8. Jackson H, Parker F: Hodgkin’s Disease and Allied Disorders. Oxford University Press,
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lative dose of alkylating agents such that two to three cycles of MOPP 9. Lukes RJ, Craver LF, Hall TC, et al: Report of the nomenclature committee. Cancer Res
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fertility after alkylating agent-based treatment is related to age at treat- and Lymphoid Tissues, 4th ed. International Agency for Research on Cancer, Lyon, 2008.
ment as well as cumulative alkylating agent dose. 263,264 The ABVD com- 11. Peters M: A study in survivals in Hodgkin’s disease treated radiologically. AJR Am J
Roentgenol 63:299–311, 1950.
bination is associated with temporary amenorrhea and azoospermia 12. Kinmonth JB: Lymphangiography in man; a method of outlining lymphatic trunks at
with full recovery noted in 50 to 95 percent of patients. 265,266 A case- operation. Clin Sci (Lond) 11:13–20, 1952.
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treated with ABVD. In contrast, no men had normospermia follow- tomy in the staging of Hodgkin’s disease. Cancer 24:709–718, 1969.
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50 percent of women. 166,167,268 Several authors have described pregnancy 15. Carbone PP, Kaplan HS, Musshoff K, et al: Report of the Committee on Hodgkin’s
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birth defects or complications of pregnancy has been seen. 264 16. Pusey W: Cases of sarcoma and of Hodgkin’s disease treated by exposures to X-rays: A
preliminary report. JAMA 38:166–196, 1902.
Thyroid dysfunction is common after neck irradiation, reaching a 17. Senn N: Therapeutical value of Roentgen ray in treatment of pseudoleukemia. NY Med
risk of 47 percent at 26 years in the Stanford series. Thus, patients at J 77:665–668, 1903.
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