ACR Appropriateness Criteria®: Follow-Up of Hodgkin's Lymphoma

ACR Appropriateness Criteria�:Follow-Up of Hodgkin’s Lymphoma

Andrea Ng, MD, Louis S. Constine, MD,Ranjan Advani, MD,

Prajnan Das, MD, MPH,Christopher Flowers, MD, MS,

Jonathan Friedberg, MD,David C. Hodgson, MD,Cindy L. Schwartz, MD,Richard B. Wilder, MD,

Lynn D. Wilson, MD, MPH,
Michael J. Yunes, MD
In the follow-up of Hodgkin’s lymphoma patients, thefocus in the first 5 years is to detect recurrence, whileafter 5 years, the focus is on limiting and detecting lateeffects of treatment. In the first 5 years post-treatment,routine history and physical and computed tomography(CT) imaging (more frequent in the first 2 years) aregenerally appropriate. However, there are limited datato support the role of positron emission tomographyscanning as routine follow-up. Beyond 5 years post-treatment, annual history and physical is appropriate,although there is no longer a role for routine imagingfor recurrences. Women irradiated to the chest area ata young age (<35) would benefit from annual mam-mogram screening given the increased breast cancerrisk. Magnetic resonance imaging can be considered,
although there is a lack of data supporting its role in this
The American College of Radiology seeks and encourages collaboration with other organizations on the development ofthe ACR Appropriateness Criteria through society representation on expert panels. Participation by representatives fromcollaborating societies on the expert panel does not necessarily imply society endorsement of the final document.Copyright © 2010 American College of Radiology. Reprinted with permission of the American College of Radiology.

Curr Probl Cancer 2010;34:211-227.0147-0272/$34.00 � 0doi:10.1016/j.currproblcancer.2010.04.007

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population. Low-dose chest CT for lung cancer screening inpatients with history of mediastinal irradiation and/oralkylating chemotherapy exposures and a smoking his-tory can be considered, although data on its utility islacking. Cardiac screening with echocardiogram and ex-ercise tolerance tests in patients with history of mediastinalirradiation and/or adriamycin exposure may be appro-priate, although the optimal screening interval woulddepend on mediastinal dose, adriamycin dose, presenceof other cardiac risk factors and findings at the baselinescreening. Patients at risk for cardiac disease due totreatment exposure would also benefit from lipid screen-ing every 1-3 years.

ummary of Literature Review

R outine follow-up evaluation of patients after treatment forHodgkin’s lymphoma serves several functions. Detection ofrelapse is the most important in the first 5 years after treatment.

eyond 5 years, the focus is on monitoring for late effects of therapy.

etection of RelapseHodgkin’s lymphoma remains the main cause of patient death during

he first 10-15 years of follow-up.1-3 Routine follow-up studies are usedo detect relapsed disease so that salvage therapy can be instituted in aimely manner.Most relapses occur within the first 5 years of treatment.1-5 As part of

ollow-up to detect recurrences, in addition to interim history (Hx) andhysical examination (PE), radiographic tests that have been advocatednclude chest x-ray (CXR), computed tomography (CT), and functionalmaging, including positron emission tomography (PET). Blood workommonly performed includes complete blood count (CBC), erythrocyteedimentation rate (ESR), lactate dehydrogenase (LDH), and chemistryanel (CHEM).Interim Hx appears to be a valuable follow-up tool in detecting relapsef Hodgkin’s lymphoma. In their review of the early-stage Hodgkin’symphoma patients treated at Stanford, Torrey et al3 found that 55% (59f 107) of the detected relapses were discovered on the basis of the Hx,ith the most commonly reported symptom being a new lump, followedy constitutional symptoms (fever, night sweats, weight loss) and pain. In
series from Christie Hospital in Manchester, England, Radford et al2
12 Curr Probl Cancer, May/June 2010

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ound that 81% (30 of 37) of relapses were diagnosed in patients whoeported symptoms, with the most common symptoms being a new lump,ollowed by cough, night sweats, and weight loss. Dryver et al4 fromanada found that 45% (10 of 22) of relapses stemmed from patientoncerns and 18% (4 of 22) from physician concerns. PE also plays anmportant role. In the Stanford series, 14% (15 of 107) of the relapsesere detected by PE. In the Manchester series, 5% (2 of 37) of relapsesere detected by PE. CXR is also useful in detecting recurrence ofodgkin’s lymphoma. In the Stanford series, 23% (24 of 107) of relapsesere detected by CXR. In the Manchester series, 5% (2 of 37) of relapsesere detected by CXR. In the series from Canada, 18% (4 of 22) of

elapses were detected by CXR.Limited data are available on the role of routine blood work in detecting

elapses. In the Stanford series,3 only 1 relapse was detected by anlevated ESR. CBC, CHEM, and serum copper did not detect any relapse.n the series from Canada,4 abnormal laboratory findings picked up theame number of relapses as CT scans (2 of 22, 9%) though at a lower cost.CT scan is routinely included in the follow-up of Hodgkin’s lymphomaatients. In contrast, a more recent study from University of Pennsylvaniahat included 40 patients with relapsed lymphoma (23 were Hodgkin’symphoma), 22 (55%) relapses were detected with surveillance imagingnd 18 (45%) were detected by clinical findings.6 Whether early radio-raphic detection of asymptomatic relapses has an impact on survival,owever, is unknown. Basciano et al7 from Memorial Sloan-Ketteringancer Center identified 94 patients with relapsed Hodgkin’s lymphomand determined that in 36 patients (38%) the relapses were detected bysymptomatic surveillance scans, and in 58 patients (62%) the relapsesere diagnosed based on clinical symptoms or findings. The prognostic

isk group distribution at relapse was comparable between the 2 groups.urthermore, at a median follow-up of 7.4 years, there were no significantifferences in 5-year failure-free survival (58.4% vs 59.3%, P � 0.9) and

overall survival (62.4% vs 73.3%, P � 0.6) between patients withasymptomatic relapses detected by surveillance scans and those withclinically evident relapses. A cost-effectiveness analysis using Markovmodeling techniques questioned the cost-effectiveness of annual CTfollow-up and showed that with adjustment for quality of life, annual CTin early-stage patients is associated with a decrease in quality-adjustedlife expectancy.8

Functional imaging studies, in particular PET, are increasingly per-ormed as part of follow-up. Most of the initial studies focused on the
ffectiveness of post-therapy functional imaging in predicting relapses,
urr Probl Cancer, May/June 2010 213

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howing that PET has a higher specificity than CT in predictingelapses.9,10 The superior specificity of PET compared with conventionalmaging methods in these studies reflects the ability of PET to detectctive disease in abnormal residual masses on CT post-treatment. Theseesults suggest that PET may be a useful test for baseline evaluation afterrst-line therapy and can help identify patients with active residualisease in whom further therapy may be needed. A cost-effectivenessnalysis based on 50 patients with unconfirmed complete remissionCRu) or partial response (PR) after first-line therapy showed that theerformance of PET in these patients saves costs by limiting the numberf patients requiring biopsies, although the comparison may be biasedince the assumption was that all patients in CRu/PR will undergo aiopsy if PET is not performed.11

Limited data are available for addressing the utility of PET as part ofoutine follow-up imaging. In the revised response criteria for malignantymphoma published in 2007, it was stated that there were insufficientata at that time to recommend PET as routine follow-up in lymphomaatients.12 More recent studies evaluated the use of surveillance PET aftern initial negative post-treatment PET, and yielded somewhat conflictingesults. Zinzani et al5 prospectively followed 421 patients (160 withodgkin’s lymphoma) who had a negative post-treatment baseline PET.atients underwent PET scans every 6 months for the first 2 years, and

hen annually after 2 years. In the 160 Hodgkin’s lymphoma patients, 51elapses were detected at a mean follow-up of 41 months (41 based onositive PET, 11 inconclusive on PET). Fourteen (27%) of the relapsesere missed by CT, and 16 (31%) were missed by clinical signs or

ymptoms. The findings led the authors’ to conclude that PET is a validool for follow-up of these patients. Of note, in this study, the detectedelapses were mostly in the 35 patients with unfavorable disease, defineds having positive PET findings after 2 cycles of chemotherapy. Twenty-ix (74%) of these patients relapsed (12, 12, and 2 relapses picked up athe 6-, 12-, and 18-month scans, respectively), suggesting that PETollow-up may be of greater value in these high-risk patients. In a studyy Mocikova et al13 in 94 Hodgkin’s lymphoma patients with negativeET findings after therapy, 155 regular follow-up PET scans were carriedut in 67 patients, the timing of which was based on the physician’secision. There were 18 cases of positive PET findings, 6 of which withonfirmed malignancies (5 Hodgkin’s lymphoma relapses and 1 lungancer). The finding that regular follow-up PET scans correctly identifiedumor in only 6 (3.9%) of the 155 PET studies led the authors to conclude
hat regular follow-up with PET scans in PET-negative patients at the end

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f therapy is not indicated. However, in patients with clinical findingsuspicious for relapse, PET scan may be of value.In a study from the Dana-Farber Cancer Institute14 on 45 Hodgkin’s

ymphoma patients with a negative PET scan after therapy, patients wereollowed with CT or PET/CT at regular intervals. The surveillancemaging detected 4 asymptomatic relapses, all of which had CT ororresponding CT abnormalities. In addition, 14 (31%) patients hadalse-positive findings leading to additional scans or biopsies. It washerefore concluded that PET had no clinical utility in the surveillance ofatients with Hodgkin’s lymphoma in remission.Investigators from Stanford University reported on their experienceith surveillance PET/CT in 113 Hodgkin’s lymphoma patients after a

omplete response to primary therapy.15 A total of 326 surveillanceET/CT scans were performed within the first 5 years after treatment.mong the 30 positive scans, 14 were true positives, yielding a positiveredictive value of only 47% and an overall recurrence detection rateith PET/CT of 4%. Moreover, 86% of the relapses occurred in therst year. Although 75% of the PET/CT-detected relapses were insymptomatic patients, the impact of early detection of asymptomaticelapse on salvage outcome is not clear. These data therefore also doot support the routine use of PET/CT surveillance, especially beyondhe first year (Tables 1-3).

etection of Second MalignanciesNumerous studies have demonstrated that patients who surviveodgkin’s lymphoma are at increased risk for second neoplasms. Solid

umors comprise most cases of second malignancies, with the mostommon ones being breast cancer and lung cancer.16

Breast cancers after Hodgkin’s lymphoma typically occur after a longatency of 10-15 years. They are associated with young age at irradiation,nd premature menopause has a protective effect. A significant radiationose–response relationship has been demonstrated,17-19 and recent studieslso showed a significant relationship between breast cancer risk andadiation field size.20,21

Mammography has been shown to be an effective tool for screeningven among these young women. In a study by Yahalom et al22 81% of7 women with breast cancer after Hodgkin’s lymphoma had mammo-raphic abnormalities of a mass and/or microcalcifications. Diller et al23

rospectively evaluated the utility of mammography in 90 femaleurvivors of Hodgkin’s lymphoma. During the study period, 10 women
eveloped 12 breast cancers, all of which were evident on mammogram.

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he high frequency of mammographically detected abnormalities sup-orts the value of mammographic screening in these patients. In a studyn breast cancer after Hodgkin’s lymphoma, Wolden et al24 found that theroportion of patients with early-stage breast cancer was higher in caseshat were diagnosed after 1990, which may be due to the more frequentse of mammography screening in the more recent era. A study fromrincess Margaret Hospital performed annual breast cancer surveillance,ostly with mammography, in 100 female survivors of Hodgkin’s

ymphoma.25 With 855 person-years of follow-up, 12 cases of breastancer were diagnosed; 7 presented with palpable mass (4 with negativeammogram in the preceding 6-12 months, 1 had indeterminate mam-ogram findings, 2 had deferred screening) and 5 were detected byammogram, 4 of which were ductal carcinoma in situ detected by

alcifications. It was noted that 52% of screened women had moderate to

ABLE 1. Variant 1: 22-year-old male with stage IIA supradiaphragmatic Hodgkin’s lymphomaESR 8), treated with ABVD �4 (PET/CT after 2 cycles) followed by involved-field radiotherapyIFRT), now 1 month post-treatment

Procedure Rating* Comments

istory and physical examination every2-4 mo for 2 y, then every 6 mo for3 y, then yearly

9

hest x-ray every 6 mo for 2 y, then yearlyfor 3 y

6 Unless chest CT performed

T chest abdomen and pelvis every 6 mofor 2 y, then yearly for 3 y

7 Frequency of relapsediminishes after 2 y

hole body PET/CT every 6 mo for 2 y,then yearly for 3 y

2

hole body PET/CT at 6 mo—if negativethen CT chest abdomen and pelvisevery 6 mo for 2 y, then yearly for 3 y

3 Likely low yield given negativePET/CT after 2 cycles ofABVD

aboratory testsCBC 1-2 times per year 7Chemistry panel 1-2 times per year No consensus No data to support performing

this test in favorablepatients

Thyroid panel yearly 8 If neck included in RT fieldESR 1-2 times per year 5

Patient Education and CounselingIncreased long-term risk of second

malignancy and cardiac disease8

Regular exercise 9Healthy diet 9Smoking cessation if current smoker 9

*Rating scale: 1-3, usually not appropriate; 4-6, may be appropriate; 7-9, usually appropriate.

xtremely dense breast tissue and that these women were more likely to


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eceive adjuvant breast magnetic resonance imaging (MRI). Similarly inStanford study26 99 mammograms of female Hodgkin’s lymphoma

urvivors were secondarily reviewed, and 60% were noted to haveigh-density breast tissue, which was also associated with a higherrequency of recall for further imaging.Breast MRI has been shown to have a higher sensitivity than mammog-

aphy in genetically predisposed women.27 The American Cancer Societyecommends annual breast MRI as an adjunct to mammogram screeningn women who had received therapeutic radiation to the chest at age 30 orounger. Similarly, in the ACR practice guideline for MRI of the breast,ne of the indications for MRI screening included a history of mantlerradiation for Hodgkin’s lymphoma.28 However, these recommendationsre expert consensus-based rather than direct evidence-based.29

ABLE 2. Variant 2: 28-year-old female with stage IIBX supradiaphragmatic Hodgkin’s lymphomaESR 30), treated with ABVD �6 (residual PET avidity after 2 cycles of ABVD, avidity resolved after

cycles of ABVD) followed by IFRT, now 1 month post-treatment


istory and physical examination every 2-4 mofor 2 y, then every 6 mo for 3 y, then yearly

9

hest x-ray every 6 mo for 2 y, then yearly 6 Unless chest CTperformed

T chest abdomen and pelvis every 6 mo for 2 y,then yearly for 3 y

8

hole body PET/CT every 6 mo for 2 y, thenyearly for 3 y

2

hole body PET/CT at 6 mo—if negative then CTchest abdomen and pelvis every 6 mo for2 y, then yearly for 3 y

5

aboratory testsCBC 1-2 times per year 8Chemistry panel 1-2 times per year No consensus No data to support

performing this testin favorablepatients

Thyroid panel yearly 8 If neck included in RTfield

ESR 1-2 times per year 7Patient Education and CounselingIncreased long-term risk of second malignancy

and cardiac disease9

Monthly self-breast examination 9Regular exercise 9Healthy diet 9Smoking cessation if current smoker 9

Rating scale: 1-3, usually not appropriate; 4-6, may be appropriate; 7-9, usually appropriate.

Lung cancer is another well-documented second malignancy after


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odgkin’s lymphoma. In addition to radiation therapy, prior chemother-py exposure (alkylating agents in particular) significantly increases theung cancer risk in a dose-dependent manner.30-32 Several studies showedhat tobacco use further adds to the risk of lung cancer after Hodgkin’symphoma.31-33 In a case-control study by Travis et al,32 survivors ofodgkin’s lymphoma who did not have more than 5 Gy of radiation

xposure and had never been exposed to alkylating agents had a 7-foldreater risk of lung cancer than survivors who had been treated withadiation therapy and alkylating agents. However, among those with thereatment exposures as well as tobacco exposure, there was a 49-foldncreased risk, suggesting a multiplicative interaction between the alky-ating agents and/or radiation with tobacco use. Unlike breast cancer, therognosis of lung cancer after Hodgkin’s lymphoma is poor, with a

ABLE 3. Variant 3: 68-year-old male with stage IA Hodgkin’s lymphoma with right cervicalnvolvement (ESR 12), treated with ABVD �4 (PET/CT after 4 cycles) followed by IFRT, now 1onth post-treatment


istory and physical examination every2-4 mo for 2 y, then every 6 mo for3 y, then yearly

9

hest x-ray every 6 mo for 2 y, thenyearly

6 Unless chest CT performed

T neck chest abdomen and pelvis every6 mo for 2 y, then yearly for 3 y

7

hole body PET/CT every 6 mo for 2 y,then yearly for 3 y

2

hole body PET/CT at 6 mo—if negativethen CT chest abdomen and pelvisevery 6 mo for 2 y, then yearly for 3y

3

aboratory TestsCBC 1-2 times per year 7Chemistry panel 1-2 times per year No consensus No data to support performing

this test in favorablepatients

Thyroid panel yearly 8ESR 1-2 times per year 5

atient Education and CounselingIncreased long-term risk of second


Regular exercise 9Healthy diet 9Smoking cessation if current smoker 9

Rating scale: 1-3, usually not appropriate; 4-6, may be appropriate; 7-9, usually appropriate.

edian survival of only about 1 year.34 Given the significantly increased


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isk of lung cancer after Hodgkin’s lymphoma, especially among smok-rs, and the associated poor prognosis, there may be a potential role forcreening and early detection of lung cancer in high-risk survivors. Aost-effectiveness analysis had suggested that annual low-dose chest CTcreening may be a cost-effective strategy among survivors who aremokers.35

etection of Nonmalignant Late Effects ofreatmentA number of studies have shown that patients who have been cured ofodgkin’s lymphoma are at significantly increased risk of death from

ardiac disease compared with the normal population.19,34,36,37

A wide spectrum of radiation-induced cardiovascular disease has beendentified in asymptomatic survivors of Hodgkin’s lymphoma, includingericardial disease, coronary artery disease, cardiomyopathy, valvularisease, arrhythmia, and autonomic dysfunction.38

The major contributor to the excess risk of cardiac mortality afterodgkin’s lymphoma is coronary artery disease, accounting for two-

hirds of all cases of fatal cardiac events in survivors of Hodgkin’symphoma. The main risk factor is mediastinal irradiation, and a signif-cant dose–response relationship has been shown.39-41 Presence of otherraditional cardiac risk factors further increases the risk of cardiovascularisease after Hodgkin’s lymphoma.39,41,42 There may be a role forcreening for and treatment of modifiable cardiac risk factors. An analysisy Chen et al43 suggests that lipid screening every 3 years would be theost cost-effective strategy in this population.The Stanford group prospectively evaluated the role of cardiac screen-

ng in asymptomatic Hodgkin’s lymphoma survivors with Hx of medi-stinal irradiation. A total of 294 patients at a median of 15 yearsost-treatment were included. In the first publication of the study, therevalence of valvular abnormalities was found to increase significantlyith increasing follow-up time, most of which were rarely picked up by

uscultation.44 Based on the findings, it was estimated that the number ofchocardiography screenings needed to identify a candidate for endocar-itis prophylaxis decreased dramatically with time following irradiation:3 for patients at 2-10 years, 4 for those at 11-20 years, and 1.6 for thoseore than 20 years, suggesting that echocardiography screening may be

eneficial, particularly in those who received their radiation treatment10 years earlier. However, the optimal screening interval is unclear, and

ikely needs to be individualized based on treatment-related and host-
elated cardiac risk factors.

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The same group subsequently reported on the high prevalence ofiastolic dysfunction based on the screening,45 with increased incidenceor those who are older, for those who have hypertension, diabetes, orall motion abnormalities, and for those with a longer latency period

rom radiation treatment to screening. For patients who had completedadiation therapy 11-20 years earlier and �20 years earlier, 15% and3%, respectively, had mild to moderate diastolic dysfunction. Further-ore, the presence of diastolic dysfunction was significantly associatedith increased risk of deaths or events due to coronary artery disease. In

he most recent report from the same group,46 14% were found to haveerfusion defects, impaired wall motion, or both on stress testing. Basedn the results, 40 patients (14%) underwent coronary angiography. Thengiography showed � 50%, � 50%, and no stenosis in 55%, 22.5%, and2.5% of patients, respectively. Because of the screening, 7 of thesesymptomatic patients (2.4%) underwent bypass graft surgery. In addi-ion, 23 patients (8%) subsequently developed coronary events during aedian of 6.5 years of follow-up, including 10 cases of acute myocardial

nfarctions. Of note, the median dose to the mediastinum among patientsncluded in this Stanford screening study was 44 Gy (range, 35-54.6 Gy),hich are doses that are considerably higher than those used in currentractice.In a prospective cardiac screening study by Adams et al47 the incidencef asymptomatic cardiac disease in 48 survivors of childhood Hodgkin’symphoma was reported. The median age of the study population at theime of initial therapy was 16.5 years, and the median dose received was0 Gy. The median follow-up time was 14.3 years. On echocardiogram,2% were found to have significant valve defects, 75% had conductionefects, and 22% had echocardiographic changes suggestive of restrictiveardiomyopathy. Aortic regurgitation was found to be associated with aecreased physical component score (PCS) on the SF-36 test (r �0.371, P � 0.011). A decreased peak myocardial oxygen uptake during

xercise (VO2max), a predictor of mortality in heart failure, was associ-ted with increased fatigue (r � �0.35, P � 0.02), increased shortness ofreath (r � �0.35, P � 0.02) and decreased PCS (r � 0.554, P �

0.00017). These findings suggest that late effects of treatment cancontribute to the increased fatigue level seen in long-term Hodgkin’slymphoma survivors. In addition, in survivors with symptoms of fatigue,evaluation for underlying cardiac disease should be considered.

Noncoronary artherosclerotic disease has also been identified in long-term Hodgkin’s lymphoma survivors. In a childhood cancer survivor
study, compared with siblings, the relative risk of stroke in Hodgkin’s

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ymphoma survivors treated with mantle irradiation was 5.6.48 However,he absolute excess risk was only 109.8 per 100,000 person-years (or 1ase per 100 patients followed for 10 years). It was estimated that at least82 carotid duplex screening ultrasound examinations need to be per-ormed to prevent a stroke, and it is concluded that there was no role foruch screening. Hull et al41 found a significant dose–response relationshipor noncoronary artherosclerotic disease in Hodgkin’s lymphoma survivors.he median doses to the low neck in patients with or without subclaviantenosis were 44 and 36 Gy (P � 0.002), respectively. Smoking and diabetesere also found to be associated with an increased risk of noncoronary

rtherosclerotic disease. In a cohort study by De Bruin et al49 Hodgkin’symphoma survivors at a median of 17.5 years out from treatment had a.2-fold increase I risk of stroke and a 3.1-fold increase in risk of transientschemic attack compared with the normal population. However, similaro the National Cancer Institute’s Childhood Cancer Survivor Study, thebsolute excess risk was also low, at 9-12 per 10,000 person-years0.9-1.2 cases per 100 patients followed for 10 years). Because of itsarity, it was also concluded that screening for carotid disease in thisopulation is not indicated.Irradiation to the upper mediastinum and low neck can result in thyroid

bnormalities. An analysis of patients treated for Hodgkin’s lymphoma attanford demonstrated that the 20-year actuarial risk of thyroid abnormalityas 50%,50 with 90% of the cases being hypothyroidism. Fifty-seven percentf patients with primary hypothyroidism had subclinical disease detectedy an elevated serum thyroid-simulating hormone (TSH) level with aormal FT4 level. The greatest risk of hypothyroidism occurred duringhe first 5 years after treatment, but new cases continued to emergeeyond 20 years after Hodgkin’s lymphoma. In a study by Sklar et al51

mong pediatric Hodgkin’s lymphoma survivors, risk factors for theevelopment of hypothyroidism included increasing radiation dose, olderge at diagnosis, and female gender.Acute radiation pneumonitis occurs in 3%-10% of patients after mediasti-al irradiation.52-54 Lung fibrosis as a late effect can result in chronichortness of breath and contribute to fatigue symptoms in long-term survi-ors.55 In the era of combined-modality therapy, the combination ofleomycin-based chemotherapy with mediastinal irradiation can furtherotentiate lung toxicity.56,57 In a study that prospectively measured theulmonary function of Hodgkin’s lymphoma patients during and afterleomycin-based chemotherapy with or without mediastinal radiotherapy,
ersistently reduced percentage of predicted carbon monoxide diffusing

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ABLE 4. Variant 4: 32-year-old female with history of stage IIA Hodgkin’s lymphoma with lefteck and mediastinal involvement, treated with ABVD �4 followed by IFRT completing treatment 5ears ago


istory and physical examinationyearly

9 Including thyroid examination andbreast examination

hest x-ray yearly 5 Unless chest CT performedT chest abdomen and pelvis yearly 3creening exercise tolerance test and

echocardiogram only ifsymptomatic

6 Screening intervals depending onmediastinal irradiation,Adriamycin dose, other riskfactors, and findings at thebaseline screening

creening exercise tolerance test andechocardiogram beginning 5 yafter treatment

5 Screening intervals depending onmediastinal irradiation,Adriamycin dose, other cardiacrisk factors and findings at thebaseline screening

creening exercise tolerance test andechocardiogram beginning 10 yafter treatment

6 Screening intervals depending onmediastinal irradiation,Adriamycin dose, other cardiacrisk factors and findings at thebaseline screening

early mammography beginning 8-10 yafter treatment

8

early mammography and breast MRIbeginning 8-10 y after treatment

7

early CT chest beginning 5 y aftertreatment

2 For lung cancer screening

early CT chest beginning 5 y aftertreatment only if smoker orsmoking history

No consensus Lack of data

aboratory TestsCBC yearly No consensus Lack of dataChemistry panel yearly No consensus No data to support performing

this test in favorable patientsThyroid panel yearly 8Lipid profile every 1-3 y 8

atient Education and CounselingIncreased long-term risk of second


Monthly self-breast examination 7Regular exercise 9Healthy diet 9Smoking cessation if current

smoker9

*Rating scale: 1-3, usually not appropriate; 4-6, may be appropriate; 7-9, usually appropriate.


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apacity (% DLCO) at 1 year was significantly associated with radiationose and a smoking history.53

Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD), the cur-ently most widely accepted systemic therapy for Hodgkin’s lymphoma, doesot appear to affect gonadal function.58,59 However, the newer, moreggressive regimen—bleomycin, etoposide, doxorubicin, cyclophospha-ide, vincristine, procarbazine, and prednisone (BEACOPP) for patientsith unfavorable or advanced-stage disease—is associated with a signif-

cant risk of continued amenorrhea in women and azoospermia inen.60,61 In addition, for patients with infradiaphragmatic Hodgkin’s

ymphoma, who comprise 5%-10% of all early-stage patients, radiationreatment to the pelvis may affect patients’ reproductive function. Four-6y of fractionated radiation therapy to the testes will result in permanent

zoospermia in most men. After 8-10 Gy of fractionated radiation therapyo the ovaries, most women will develop ovarian failure.Other late effects of Hodgkin’s lymphoma treatment include immunosup-ression, fatigue, psychological distress, and social maladaptation.62,63

wareness of the potential consequences of treatment is necessary forhysicians conducting patient follow-up to detect problems at the earliestossible time (Table 4).

isclaimer:The ACR Committee on Appropriateness Criteria® and its expert panelsave developed criteria for determining appropriate imaging examina-ions for diagnosis and treatment of specified medical condition(s). Theseriteria are intended to guide radiologists, radiation oncologists andeferring physicians in making decisions regarding radiologic imag-ng and treatment. Generally, the complexity and severity of aatient’s clinical condition should dictate the selection of appropriatemaging procedures or treatments. Only those exams generally usedor evaluation of the patient’s condition are ranked. Other imagingtudies necessary to evaluate other co-existent diseases or otheredical consequences of this condition are not considered in thisocument. The availability of equipment or personnel may influencehe selection of appropriate imaging procedures or treatments. Imag-ng techniques classified as investigational by the FDA have not beenonsidered in developing these criteria; however, study of newquipment and applications should be encouraged. The ultimateecision regarding the appropriateness of any specific radiologic
xamination or treatment must be made by the referring physician and

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adiologist in light of all the circumstances presented in an individualxamination.

REFERENCES1. Jerusalem G, Beguin Y, Fassotte MF, Belhocine T, Hustinx R, Rigo P, et al. Early

detection of relapse by whole-body positron emission tomography in the follow-upof patients with Hodgkin disease. Ann Oncol 2003;14:123-30.

2. Radford JA, Eardley A, Woodman C, Crowther D. Follow up policy after treatmentfor Hodgkin disease: too many clinic visits and routine tests? A review of hospitalrecords. BMJ 1997;314:343-6.

3. Torrey MJ, Poen JC, Hoppe RT. Detection of relapse in early-stage Hodgkindisease: role of routine follow-up studies. J Clin Oncol 1997;15:1123-30.

4. Dryver ET, Jernstrom H, Tompkins K, Buckstein R, Imrie KR. Follow-up ofpatients with Hodgkin disease following curative treatment: the routine CT scan isof little value. Br J Cancer 2003;89:482-6.

5. Zinzani PL, Stefoni V, Tani M, Fanti S, Musuraca G, Castellucci P, et al. Role of[18F] fluorodeoxyglucose positron emission tomography scan in the follow-up oflymphoma. J Clin Oncol 2009;27:1781-7.

6. Xavier MF, Schuster SJ, Andreadis C, et al. Detection of relapse in diffuse largeB-cell lymphoma (DLBCL) and Hodgkin’s lymphoma (HL): observations andimplications for post-remission radiologic surveillance. ASH Annual MeetingAbstracts 2006;108:2428.

7. Basciano BA, Moskowitz C, Zelenetz AD. Impact of routine surveillance imagingon the outcome of patients with relapsed Hodgkin lymphoma. ASH AnnualMeeting Abstracts 2009;114:1558.

8. Guadagnolo BA, Punglia RS, Kuntz KM, Mauch PM, Ng AK. Cost-effectivenessanalysis of computerized tomography in the routine follow-up of patients afterprimary treatment for Hodgkin disease. J Clin Oncol 2006;24:4116-22.

9. Hueltenschmidt B, Sautter-Bihl ML, Lang O, Maul FD, Fischer J, MergenthalerHG, et al. Whole body positron emission tomography in the treatment of Hodgkindisease. Cancer 2001;91:302-10.

0. Mikosch P, Gallowitsch HJ, Zinke-Cerwenka W, Heinisch M, Pipam W, Eibl M, etal. Accuracy of whole-body 18F–FDP-PET for restaging malignant lymphoma.Acta Med Austriaca 2003;30:41-7.

1. Cerci JJ, Trindade E, Pracchia LF, Pitella FA, Linardi CC, Soares J Jr, et al. Costeffectiveness of positron emission tomography in patients with Hodgkin’s lym-phoma in unconfirmed complete remission or partial remission after first-linetherapy. J Clin Oncol 2010;28:1415-21.

2. Cheson BD. The International Harmonization Project for response criteria inlymphoma clinical trials. Hematol Oncol Clin North Am 2007;21:841-54.

3. Mocikova H, Obrtlikova P, Vackova B, Trneny M. Positron emission tomographyat the end of first-line therapy and during follow-up in patients with Hodgkinlymphoma: a retrospective study. Ann Oncol 2009, Epub ahead of print.

4. Zuckerman D, Lacasce A, Jacobsen E, et al. High false positive rate with the useof CT and FDG-PET in post-remission surveillance for Hodgkin lymphoma. ASHAnnual Meeting Abstracts 2007;110:2327.

5. Maeda LS, Horning SJ, Iagaru AH, et al. Role of FDG-PET/CT surveillance for


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patients with classical Hodgkin’s disease in first complete response: The StanfordUniversity Experience. ASH Annual Meeting Abstracts 2009;114:1563.

6. Hodgson DC, Gilbert ES, Dores GM, Schonfeld SJ, Lynch CF, Storm H, et al.Long-term solid cancer risk among 5-year survivors of Hodgkin’s lymphoma.J Clin Oncol 2007;25:1489-97.

7. Inskip PD, Robison LL, Stovall M, Smith SA, Hammond S, Mertens AC, et al.Radiation dose and breast cancer risk in the childhood cancer survivor study. J ClinOncol 2009;27:3901-7.

8. Travis LB, Hill DA, Dores GM, Gospodarowicz M, van Leeuwen FE, Holowaty E,et al. Breast cancer following radiotherapy and chemotherapy among young womenwith Hodgkin disease. J Am Med Assoc 2003;290:465-75.

9. van Leeuwen FE, Klokman WJ, Stovall M, Dahler EC, van’t Veer MB, NoordijkEM, et al. Roles of radiation dose, chemotherapy, and hormonal factors in breastcancer following Hodgkin’s disease. J Natl Cancer Inst 2003;95:971-80.

0. De Bruin ML, Sparidans J, Van’T Veer MB, Noordijk EM, Louwman MW, ZijlstraJM, et al. Breast cancer risk in female survivors of Hodgkin’s lymphoma: lowerrisk after smaller radiation volumes. J Clin Oncol 2009;27:4239-46.

1. Franklin J, Pluetschow A, Paus M, Specht L, Anselmo AP, Aviles A, et al. Secondmalignancy risk associated with treatment of Hodgkin’s lymphoma: meta-analysisof the randomised trials. Ann Oncol 2006;17:1749-60.

2. Yahalom J, Petrek JA, Biddinger PW, Kessler S, Dershaw DD, McCormick B, etal. Breast cancer in patients irradiated for Hodgkin’s disease: a clinical andpathologic analysis of 45 events in 37 patients. J Clin Oncol 1992;10:1674-81.

3. Diller L, Medeiros Nancarrow C, Shaffer K, Matulonis U, Mauch P, Neuberg D, etal. Breast cancer screening in women previously treated for Hodgkin’s disease: aprospective cohort study. J Clin Oncol 2002;20:2085-91.

4. Wolden SL, Hancock SL, Carlson RW, Goffinet DR, Jeffrey SS, Hoppe RT. Managementof breast cancer after Hodgkin’s disease. J Clin Oncol 2000;18:765-72.

5. Lee L, Pintilie M, Hodgson DC, Goss PE, Crump M. Screening mammography foryoung women treated with supradiaphragmatic radiation for Hodgkin’s lymphoma.Ann Oncol 2008;19:62-7.

6. Kwong A, Hancock SL, Bloom JR, Pal S, Birdwell RL, Mariscal C, et al.Mammographic screening in women at increased risk of breast cancer aftertreatment of Hodgkin’s disease. Breast J 2008;14:39-48.

7. Warner E, Messersmith H, Causer P, Eisen A, Shumak R, Plewes D. Systematicreview: using magnetic resonance imaging to screen women at high risk for breastcancer. Ann Intern Med 2008;148:671-9.

8. American College of Radiology. ACR Practice Guideline for the performance ofcontrast-enhanced magnetic resonance imaging (MRI) of the breast Available at:http://www.acr.org/SecondaryMainMenuCategories/quality_safety/guidelines/breast/mri_breast.aspx. Accessed January 7, 2010.

9. Saslow D, Boetes C, Burke W, Harms S, Leach MO, Lehman CD, et al. AmericanCancer Society guidelines for breast screening with MRI as an adjunct tomammography. CA Cancer J Clin 2007;57:75-89.

0. Swerdlow AJ, Barber JA, Hudson GV, Cunningham D, Gupta RK, Hancock BW,et al. Risk of second malignancy after Hodgkin’s disease in a collaborative Britishcohort: the relation to age at treatment. J Clin Oncol 2000;18:498-509.

1. Swerdlow AJ, Schoemaker MJ, Allerton R, Horwich A, Barber JA, Cunningham D,


http://www.acr.org/SecondaryMainMenuCategories/quality_safety/guidelines/breast/mri_breast.aspx

http://www.acr.org/SecondaryMainMenuCategories/quality_safety/guidelines/breast/mri_breast.aspx

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et al. Lung cancer after Hodgkin’s disease: a nested case-control study of therelation to treatment. J Clin Oncol 2001;19:1610-8.

2. Travis LB, Gospodarowicz M, Curtis RE, Clarke EA, Andersson M, Glimelius B,et al. Lung cancer following chemotherapy and radiotherapy for Hodgkin’s disease.J Natl Cancer Inst 2002;94:182-92.

3. van Leeuwen FE, Klokman WJ, Stovall M, Hagenbeek A, van den Belt-Dusebout AW,Noyon R, et al. Roles of radiotherapy and smoking in lung cancer following Hodgkindisease. J Natl Cancer Inst 1995;87:1530-7.

4. Ng AK, Bernardo MV, Weller E, Backstrand K, Silver B, Marcus KC, et al. Secondmalignancy after Hodgkin disease treated with radiation therapy with or withoutchemotherapy: long-term risks and risk factors. Blood 2002;100:1989-96.

5. Das P, Ng AK, Earle CC, Mauch PM, Kuntz KM. Computed tomography screeningfor lung cancer in Hodgkin’s lymphoma survivors: decision analysis and cost-effectiveness analysis. Ann Oncol 2006;17:785-93.

6. Eriksson F, Gagliardi G, Liedberg A, Lax I, Lee C, Levitt S, et al. Long-termcardiac mortality following radiation therapy for Hodgkin’s disease: analysis withthe relative seriality model. Radiother Oncol 2000;55:153-62.

7. Hoppe RT. Hodgkin’s disease: complications of therapy and excess mortality. AnnOncol 1997;8:115-8 (suppl 1).

8. Carver JR, Shapiro CL, Ng A, Jacobs L, Schwartz C, Virgo KS, et al. American Society ofClinical Oncology clinical evidence review on the ongoing care of adult cancer survivors:cardiac and pulmonary late effects. J Clin Oncol 2007;25:3991-4008.

9. Glanzmann C, Huguenin P, Lutolf UM, Maire R, Jenni R, Gumppenberg V.Cardiac lesions after mediastinal irradiation for Hodgkin’s disease. RadiotherOncol 1994;30:43-54.

0. Hancock SL, Tucker MA, Hoppe RT. Factors affecting late mortality from heartdisease after treatment of Hodgkin’s disease. J Am Med Assoc 1993;270:1949-55.

1. Hull MC, Morris CG, Pepine CJ, Mendenhall NP. Valvular dysfunction andcarotid, subclavian, and coronary artery disease in survivors of Hodgkin lymphomatreated with radiation therapy. J Am Med Assoc 2003;290:2831-7.

2. Aleman BM, van den Belt-Dusebout AW, De Bruin ML, van’t Veer MB, BaaijensMH, de Boer JP, et al. Late cardiotoxicity after treatment for Hodgkin lymphoma.Blood 2007;109:1878-86.

3. Chen AB, Punglia RS, Kuntz KM, Mauch PM, Ng AK. Cost effectiveness andscreening interval of lipid screening in Hodgkin’s lymphoma survivors. J ClinOncol 2009;27:5383-9.

4. Heidenreich PA, Hancock SL, Lee BK, Mariscal CS, Schnittger I. Asymptomaticcardiac disease following mediastinal irradiation. J Am Coll Cardiol 2003;42:743-9.

5. Heidenreich PA, Hancock SL, Vagelos RH, Lee BK, Schnittger I. Diastolicdysfunction after mediastinal irradiation. Am Heart J 2005;150:977-82.

6. Heidenreich PA, Schnittger I, Strauss HW, Vagelos RH, Lee BK, Mariscal CS, et al.Screening for coronary artery disease after mediastinal irradiation for Hodgkin’sdisease. J Clin Oncol 2007;25:43-9.

7. Adams MJ, Lipsitz SR, Colan SD, Tarbell ST, Diller L, Greenbaum N, et al.Cardiovascular status in long-term survivors of Hodgkin’s disease treated withchest radiotherapy. J Clin Oncol 2004;22:3139-48.

8. Bowers DC, McNeil DE, Liu Y, Yasui Y, Stovall M, Gurney JG, et al. Stroke as


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6

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a late treatment effect of Hodgkin’s disease: a report from the Childhood CancerSurvivor Study. J Clin Oncol 2005;23:6508-15.

9. De Bruin ML, Dorresteijn LD, Van’T Veer MB, Krol AD, van der Pal HJ, KappelleAC, et al. Increased risk of stroke and transient ischemic attack in 5-year survivorsof Hodgkin lymphoma. J Natl Cancer Inst 2009;101:928-37.

0. Hancock SL, Cox RS, McDougall IR. Thyroid diseases after treatment ofHodgkin’s disease. N Engl J Med 1991;325:599-605.

1. Sklar C, Whitton J, Mertens A, Stovall M, Green D, Marina N, et al. Abnormalitiesof the thyroid in survivors of Hodgkin’s disease: data from the Childhood CancerSurvivor Study. J Clin Endocrinol Metab 2000;85:3227-32.

2. Koh ES, Sun A, Tran TH, Tsang R, Pintilie M, Hodgson DC, et al. Clinicaldose-volume histogram analysis in predicting radiation pneumonitis in Hodgkin’slymphoma. Int J Radiat Oncol Biol Phys 2006;66:223-8.

3. Ng AK, Li S, Neuberg D, Chi R, Fisher DC, Silver B, et al. A prospective study ofpulmonary function in Hodgkin’s lymphoma patients. Ann Oncol 2008;19:1754-8.

4. Tarbell NJ, Thompson L, Mauch P. Thoracic irradiation in Hodgkin’s disease:disease control and long-term complications. Int J Radiat Oncol Biol Phys1990;18:275-81.

5. Knobel H, Havard Loge J, Brit Lund M, Forfang K, Nome O, Kaasa S. Latemedical complications and fatigue in Hodgkin’s disease survivors. J Clin Oncol2001;19:3226-33.

6. Hirsch A, Vander Els N, Straus DJ, Gomez EG, Leung D, Portlock CS, et al. Effectof ABVD chemotherapy with and without mantle or mediastinal irradiation onpulmonary function and symptoms in early-stage Hodgkin’s disease. J Clin Oncol1996;14:1297-305.

7. Horning SJ, Adhikari A, Rizk N, Hoppe RT, Olshen RA. Effect of treatment forHodgkin’s disease on pulmonary function: results of a prospective study. J ClinOncol 1994;12:297-305.

8. Hodgson DC, Pintilie M, Gitterman L, Dewitt B, Buckley CA, Ahmed S, et al.Fertility among female Hodgkin lymphoma survivors attempting pregnancy fol-lowing ABVD chemotherapy. Hematol Oncol 2007;25:11-5.

9. Kulkarni SS, Sastry PS, Saikia TK, Parikh PM, Gopal R, Advani SH. Gonadalfunction following ABVD therapy for Hodgkin’s disease. Am J Clin Oncol1997;20:354-7.

0. Behringer K, Breuer K, Reineke T, May M, Nogova L, Klimm B, et al. Secondaryamenorrhea after Hodgkin’s lymphoma is influenced by age at treatment, stage ofdisease, chemotherapy regimen, and the use of oral contraceptives during therapy:a report from the German Hodgkin’s Lymphoma Study Group. J Clin Oncol2005;23:7555-64.

1. Sieniawski M, Reineke T, Nogova L, Josting A, Pfistner B, Diehl V, et al. Fertilityin male patients with advanced Hodgkin lymphoma treated with BEACOPP: areport of the German Hodgkin Study Group (GHSG). Blood 2008;111:71-6.

2. Mauch P, Ng A, Aleman B, Carde P, Constine L, Diehl V, et al. Report from theRockefellar Foundation Sponsored International workshop on reducing mortalityand improving quality of life in long-term survivors of Hodgkin’s disease: July9-16, 2003, Bellagio, Italy. Eur J Haematol Suppl 2005:68-76.

3. Ng AK, Mauch PM. Late effects of Hodgkin’s disease and its treatment. Cancer J
2009;15:164-8.

ACR Appropriateness Criteria®: Follow-Up of Hodgkin's Lymphoma

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