close

Вход

Забыли?

вход по аккаунту

?

313

код для вставкиСкачать
1687
Grading of Late Effects in Young Adult Survivors
of Childhood Cancer Followed in An Ambulatory
Adult Setting
Kevin C. Oeffinger, M.D.1
Debra A. Eshelman, C.P.N.P.2
Gail E. Tomlinson, M.D., Ph.D.3
George R. Buchanan, M.D.3
Barbara M. Foster, Ph.D.4
1
Department of Family Practice and Community
Medicine, the After the Cancer Experience (ACE)
Young Adult Program, The University of Texas
Southwestern Medical Center at Dallas, and Children’s Medical Center, Dallas, Texas.
2
Center for Cancer and Blood Disorders, the After
the Cancer Experience (ACE) Young Adult Program,
The University of Texas Southwestern Medical
Center at Dallas, and Children’s Medical Center,
Dallas, Texas.
3
Division of Hematology-Oncology, Department of
Pediatrics, the After the Cancer Experience (ACE)
Young Adult Program, The University of Texas
Southwestern Medical Center at Dallas, and Children’s Medical Center, Dallas, Texas.
4
Academic Computing Services, The University of
Texas Southwestern Medical Center at Dallas, Dallas, Texas.
Presented at Cancer Survivorship: Research Challenges and Opportunities for the New Millennium,
Bethesda, Maryland, March 8, 1999.
The statistical data analysis was supported by
funds from the Simmons Cancer Center at UT
Southwestern.
The authors would like to thank Laura Snell,
M.P.H., for her assistance with editing.
Address for reprints: Kevin C. Oeffinger, M.D.,
Department of Family Practice and Community
Medicine, The University of Texas Southwestern
Medical Center, 5323 Harry Hines Blvd., Dallas,
TX, 75235-9067.
Received April 19, 1999; revisions received August
18, 1999, and November 18, 1999; accepted November 18, 1999.
© 2000 American Cancer Society
BACKGROUND. The objective of the current study was to describe a multidisciplinary transition program for following young adult survivors of childhood cancer
in an adult-based ambulatory medical setting and to report the late effects with
grades of toxicity diagnosed in all adult survivors followed in the program.
METHODS. The study population was comprised of all young adult survivors (n ⫽
96) of childhood cancer who were seen in the After the Cancer Experience (ACE)
Young Adult Program prior to January 31, 1999. The median age of the survivors
was 22.8 years (range, 17–34 years) and the median interval from the time of cancer
diagnosis was 15.2 years (range, 6 –25 years). Primary cancer groups included:
leukemia, 33%; sarcoma, 24%; Hodgkin disease, 15%; non-Hodgkin lymphoma,
12%; Wilms’ tumor, 9%; and other, 7%. Late effects were graded using the Common
Toxicity Criteria, Version 2 (CTCv2), developed by the National Cancer Institute.
RESULTS. Approximately 69% of the patients (66 of 96) had at least 1 late effect.
Thirty-three percent of patients had a single late effect whereas 36% had ⱖ 2 late
effects. Thirty percent of patients had a CTCv2 Grade 3 or 4 late effect.
CONCLUSIONS. The current study represents an example of a successful multidisciplinary transition program in an ambulatory, adult setting for young adult survivors of childhood cancer. Late effects of cancer treatment are common in young
adult survivors, with approximately 33% being moderate to severe. Further studies
are needed to modify CTCv2 with the aim of developing a reliable and valid tool to
assess late effects in long term survivors of childhood cancer. Cancer 2000;88:
1687–1695. © 2000 American Cancer Society.
KEYWORDS: neoplasm, child, adolescence, young adult, survivors, late effects,
transition, follow-up studies, Common Toxicity Criteria.
A
s the number of childhood cancer survivors grows, attention is
increasingly being directed to the evaluation and management of
late effects or sequelae of treatment.1 Late effects range from relatively benign conditions such as radiation-induced alopecia to potentially life-threatening problems such as radiation-related breast carcinoma or anthracycline-induced cardiomyopathy.2-5 Virtually all
organ systems can be affected by either radiation, chemotherapy, or
surgery. Because our understanding of the natural history of late
effects is evolving slowly, it is important to maintain contact with and
periodically study this population of patients. Regularly scheduled
surveillance, with early detection and treatment of late effects, combined with education concerning risk modification theoretically
should impact the quality of life and long term health of adult survivors and should be investigated further.
Most adult survivors of childhood cancer are not followed on a
1688
CANCER April 1, 2000 / Volume 88 / Number 7
regular basis. Preliminary data from the National Institutes of Health funded, multicenter Childhood Cancer Survivor Study show that 51% of approximately
14,000 responding long term survivors of childhood
cancer had not been seen by a physician during the
previous 2 years for evaluation of cancer-related problems.6 A recent survey of the members of the Pediatric
Oncology Group and Children’s Cancer Group reported that 44% of responding institutions have a
mechanism for following adult survivors, but only 15%
of the programs have established a formal database
for this population.6
Multidisciplinary transition programs, combining
the expertise of pediatric oncologists with health care
providers experienced in the health needs of adult
patients, have been recommended as a possible
mechanism for the long term follow-up of childhood
cancer survivors.7-11 However, to our knowledge few
programs exist that combine these areas of expertise
in the care of adult survivors of childhood cancer.6
The purpose of the current study was to: 1) describe a multidisciplinary transition program for following young adult survivors of childhood cancer in
an adult-based ambulatory medical setting and 2) to
report the late effects with grades of toxicity diagnosed
in the first 96 adult survivors who were followed in the
program.
MATERIALS AND METHODS
After the Cancer Experience (ACE) Young Adult Program
The After the Cancer Experience (ACE) Young Adult
Program was developed in 1995 as a collaborative
effort between the Center for Cancer and Blood Disorders at Children’s Medical Center of Dallas and the
Department of Family Practice and Community Medicine at the University of Texas Southwestern. The
program was developed as an extension of the ACE
Program, a late effects program that started in 1989
and follows childhood cancer survivors age ⬍ 18 years
who are at least 24 months posttreatment. The ACE
Program collaborates with the Cancer Registry of the
Children’s Medical Center of Dallas, begun in 1990, in
tracking the status of childhood cancer survivors
treated at the institution.
Adult survivors ⱖ 18 years of age are eligible for
regular follow-up in the ACE Young Adult Program.
Patients are followed annually and examined and
screened for late effects of cancer therapy, second
malignant neoplasms, and risk factors that may contribute to the early onset of common adult health
problems. Protocols used for routine testing of asymptomatic young adult survivors of childhood cancer
seen in the ACE Young Adult Program, adapted from
current literature and modified for the patient popu-
lation, are described in Table 1. Additional laboratory,
radiographic, or other testing is performed as indicated, based on the clinical history or findings. Patient
education materials, verbal and written, have been
collected or developed within the program and are
provided for areas of concern and health risk reduction. Late effects diagnosed at each visit are maintained in a formal database, which includes patient
demographics and treatment protocols.
The ACE Young Adult Program, centered in an
adult-based ambulatory care center, is directed by a
family practice physician (K.O.) and coordinated by a
pediatric oncology nurse practitioner (D.E.). Also included on the ACE Young Adult team are two pediatric
oncologists and two other family physicians. A consulting network of adult and pediatric subspecialists
has been developed by the team and includes cardiologists, endocrinologists, a hepatologist, orthopedic
surgeons, and gynecologists. Family practice residents
rotate through the clinic and are taught the basic
components of follow-up and potential health problems of childhood cancer survivors. The team also is
active in speaking before oncologists and primary care
physicians at continuing education programs.
Patient Characteristics
All young adult survivors (n ⫽ 96) seen in the ACE
Young Adult Program prior to January 31, 1999 form
the study population. As noted in other settings, the
percentage of survivors involved in long term follow-up decreases with age. Survivors seen in this program represent approximately 25% of the childhood
cancer survivors who are at least age 18 years. To our
knowledge the exact number and demographics of all
adult survivors of childhood cancer who were treated
at the study institution are not well described prior to
the development of the cancer registry database in
1990, thus preventing comparison of the survivors followed in the ACE Young Adult Program with those
who have been lost to follow-up. The current age of
the 96 patients ranged from 18 –34 years, with a median of 22.8 years. Patients were diagnosed with childhood cancer between 1973 and 1992, at a median age
of 9.8 years (range, 1–18 years). The median interval
since diagnosis was 15.2 years (range, 6 –25 years).
Approximately 59% of the patients were males and
41% were females. Of the 96 adult survivors, 86% were
white, 8% were Hispanic, 5% were African-American,
and 1% was classified as other.
As illustrated in Table 2, the primary cancers of
the 96 young adults were acute lymphoblastic leukemia (ALL) (29%), Hodgkin disease (15%), non-Hodgkin
lymphoma (12%), osteosarcoma (9%), Wilms’ tumor
(9%), and rhabdomyosarcoma (6%). Survivors of cen-
Young Adult Survivors of Childhood Cancer/Oeffinger et al.
1689
TABLE 1
Treatment Specific Protocol for the Routine Screening of Asymptomatic Survivors Seen in the
After the Cancer Experience (ACE) Young Adult Program
Treatment
Chemotherapy
If patient received:
Actinomycin or antimetabolite
Aminoglycoside, high dose
Anthracycline
(ⱖ 300 mg/m2, or anthracycline administered prior to age 1 one year
or ⱖ 200 mg/m2 with radiation involving the chest)
BCNU, CCNU, bleomycin
Cisplatin
Corticosteroids
Cyclophosphamide
Cyclosporine
Etoposide
Nitrogen mustard, procarbazine
Vincristine
Radiation therapy
If patient received:
Cranial or craniospinal radiation
Mantle radiation
Abdominal radiation
Pelvic radiation
High dose radiation of the trunk or extremities
Surgery
If patient received:
Nephrectomy
Splenectomy
Miscellaneous
If patient received blood products before July 1992
Screening test
Frequency
ALT
Bone densitometry
Audiology
Echocardiogram
EKG
Periodically
Optional
Optional
Every 3 years
Optional
CXR
Pulmonary function tests
BUN, creatinine, magnesium
Audiology
Bone densitometry
FSH, LH, estradiol
Semen analysis
Urinalysis
Urine cytology
Bone densitometry
CBC with platelets and differential
CBC with platelets and differential
FSH, LH, estradiol
Testosterone
Semen analysis
ALT
Baseline
Baseline and as needed
Annually
Optional
Optional
Optional
Optional
Annually
Optional
Optional
Annually
Annually
Optional
Optional
Optional
Periodically
Cataract screening
Audiology
Dental screening
TSH, Free T4
Lipid profile
Bone densitometry
TSH
Lipid profile
Mammogram (females)
Plain radiographs of irradiated site
Hemoccult screening
Urinalysis
FSH, LH
Semen analysis
Plain radiographs of the irradiated sites
Periodically
Optional
Annually
Annually
Annually
Optional
Annually
Annually
Start 8 years after radiation, then annually
Optional
Annually
Annually
Optional
Optional
Optional
BUN, creatinine, urinalysis
Verify immunizations
Antibiotic prophylaxis
Annually
Annually
Optional
HIV
Anti-HCV
Baseline
Baseline
ALT: alanine aminotransferase; EKG: electrocardiogram; BCNU: carmustine; CCNU: lomustine; CXR: chest radiography; BUN: blood urea nitrogen; FSH: follicle-stimulating hormone; CBC: complete blood count with
differential; TSH: thyroid-stimulating hormone; HIV: human immunodeficiency antibody; anti-HCV: antibody to hepatitis C virus; LH: luteinizing hormone.
tral nervous system (CNS) tumors were underrepresented in this population because they are followed
separately by a multidisciplinary neurooncology team.
Treatment modalities for the primary cancer included:
chemotherapy only (22%); radiotherapy only (2%);
chemotherapy and radiotherapy (32%); chemotherapy
and surgery (17%); radiotherapy and surgery (5%); and
chemotherapy, radiotherapy, and surgery (22%).
1690
CANCER April 1, 2000 / Volume 88 / Number 7
TABLE 2
Primary Cancers in 96 Consecutive Patients Seen
in the ACE Young Adult Program
Cancer
No. of patients
Leukemia
Acute lymphoblastic leukemia
Acute myelogenous leukemia
Sarcoma
Osteosarcoma
Rhabdomyosarcoma
Other sarcomas
NHL/HD
NHL
HD
Wilms’ tumor
Other
Neuroblastoma
Langerhans’ cell histiocytosis
Hepatocellular carcinoma
Medulloblastoma
Total
32
28
4
23
9
6
8
25
11
14
9
7
3
2
1
1
96
ACE: After the Cancer Experience; NHL: non-Hodgkin lymphoma; HD: Hodgkin disease.
Grading of Late Effects
At the time of the current study, there were no universally accepted, validated, scoring systems available
for use in grading late effects resulting from all modalities of treatment. Systems have been created for
specific institutional12 or organizational13 use, but to
our knowledge have yet to be validated. The late effects normal tissue (LENT) scoring system has been
developed to grade radiation-related late effects but
does not include scoring mechanisms for late effects
secondary to surgery or chemotherapy.14-16 The Common Toxicity Criteria (CTC) was created in 1988 by the
National Cancer Institute (NCI) as an additional outcome measure to compare the acute toxicities of different treatments. In 1998, the NCI released the second version of the CTC (CTCv2), which included the
Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of
Cancer (EORTC) Late Radiation Morbidity Scoring
Scheme.17 The CTCv2 guide is a familiar, widely used
tool that grades toxicity from 0 to 4. Although CTCv2
was not developed specifically for use in grading late
effects, the majority of late effects can be scored easily
for the various organ systems or the appendixed Late
Radiation Morbidity Scoring Scheme. For these reasons, the CTCv2 scoring system was selected in the
current study to grade late effects. In Table 3, CTCv2
grading criteria of two late effects, left ventricular dysfunction and hypothyroidism, are presented as examples.
At each patient visit in the ACE Young Adult Pro-
gram, all late effects diagnosed by means of history,
physical examination, or testing are recorded in the
database. Consecutive patients seen in the program
between March 1, 1995 and January 31, 1999 were
included in the study. Retrospectively, the database
and each patient’s medical chart were reviewed independently by two of the investigators (K.O. and D.E.)
to grade the late effects recorded at the patient’s last
visit using the CTCv2. No discrepancies were found
between the medical record and the database or between retrospective toxicity scoring and objective
scoring with subsequent visits.
Subjective reports of symptoms that might overlap with other unrelated conditions, such as fatigue,
dyspepsia, and insomnia, were not included. The only
subjective symptom used for coding was pain due to
radiation, and this was graded as per the CTCv2 guidelines. Weight gain, listed as a toxicity in the constitutional symptoms category, was used only for patients
who had received cranial irradiation and who had
documented weight gain within the guidelines of
CTCv2. If a late effect secondary to radiation therapy
could not be graded in a specific organ system, it was
graded by the RTOG/EORTC Late Radiation Morbidity
Scoring Scheme. For specific late effects not listed in
the appropriate organ system category or in the Late
Radiation Morbidity Scoring Scheme, the “organ system-other” category was used and the grade was assigned as: 0: none; 1: mild; 2: moderate; 3: severe; and
4: life-threatening. For two common groups of late
effects, “Musculoskeletal” and “Infection,” the “Other”
category was modified to a more detailed format, as
shown in Table 4.
Analysis
Data were analyzed by descriptive techniques using
frequencies, percentages, means, and medians as appropriate. The Student t test was used for comparison
of survivors exposed to anthracyclines. Because of the
small population studied, differences between cancer
types were not analyzed. In addition, because the
numbers of patients seen in the first 2 years of the
program were small, comparisons over time were not
calculated.
RESULTS
Approximately 31% (30 of 96) of the patients did not
have a late effect measurable by the CTCv2 (Table 5).
Thirty percent (9 of 30) of patients without a CTCgraded late effect had an “unclassified” late effect,
including postnephrectomy (n ⫽ 6), asplenia (n ⫽ 1),
depression (n ⫽ 1), and breast fibroadenoma in the
radiation field ( n ⫽ 1).
The 66 patients (69%) with a CTCv2-graded late
Young Adult Survivors of Childhood Cancer/Oeffinger et al.
1691
TABLE 3
Examples of Late Effects Graded by Common Toxicity Criteria v2
Cardiovascular (General)
Grade
Toxicity
0
1
2
3
4
Cardiac left
ventricular
function
Normal
Asymptomatic decline of resting EF
of ⱖ 10% but ⬍ 20% of baseline
value; SF ⱖ 24% but ⬍ 30%
Asymptomatic but resting EF below LLN
for laboratory or decline of resting EF ⱖ
20% of baseline value; ⬍ 24% SF
CHF responsive
to treatment
Severe or refractory
CHF requiring
intubation
Endocrine
Grade
Toxicity
0
Hypothyroidism Absent
1
2
3
4
Asymptomatic, TSH elevated, no
therapy given
Symptomatic or thyroid replacement
treatment given
Patient hospitalized for
manifestations of
hypothyroidism
Myxedema
coma
V2: version 2; EF: ejection fraction; SF: shortening fraction; LLN: lower limits of normal; CHF: congestive heart failure; TSH: thyroid-stimulating hormone.
TABLE 4
Modified Categories of Common Toxicity Criteria v2
Musculoskeletal
Grade
Toxicity
0
1
2
3
4
Facial/skeletal
abnormality
Absent
Mild facial or skeletal abnormality
not requiring surgery and
without chronic symptoms
Moderate facial or skeletal
abnormality not
requiring surgery but
with chronic symptoms
An abnormality that is symptomatic and
interfering with activities of daily
living or requiring multiple plastic or
reconstructive surgeries
Life-threatening
or disabling
problem
Infection
Grade
Toxicity
0
1
2
3
4
Hepatitis C
Absent
Normal ALT
Persistently elevated ALT
(ⱖ 1.5 ⫻ normal)
Requiring treatment (interferon
with or without ribavirin)
With liver failure
V2: version 2; ALT: alanine aminotransferase.
effect had a total of 115 late effects. Approximately
33% of patients (32 of 96) had a single late effect
whereas 35% had ⱖ 2 late effects. Twenty patients
(24%) were diagnosed with an asymptomatic late effect of Grade 2– 4 (e.g., cardiomyopathy or hepatitis C)
that previously was undetected and that subsequently
required therapy or closer surveillance. Late effects
diagnosed in the 66 patients are listed by involved
organ system in Table 6.
Twenty-nine of the survivors (30%) had a Grade 3
or 4 late effect that could be separated into life-threatening toxicities or sequelae predisposing to long term
emotional distress. The CTCv2 categories of the ten
patients who had potentially life-threatening toxicities
were: Secondary Malignancy (synovial sarcoma and
late [10 years] recurrence of Hodgkin disease); Cardiovascular (cardiomyopathy with congestive heart failure); Infection (hepatitis C with chronic active hepatitis requiring treatment or with liver failure); and
Neurology (chronic seizure disorder). The other 19
1692
CANCER April 1, 2000 / Volume 88 / Number 7
TABLE 5
Late Effects Graded as per CTCV2
Category
Percent
No.
Patients with:
No CTCv2 late effecta
Late effect
Single late effect
Multiple late effects (ⱖ 2)
Grade 3 or 4 toxicity
31%
69%
33%
35%
30%
30/96
66/96
32/96
34/96
29/96
CTCv2: Common Toxicity Criteria version 2.
a
Approximately 30% (9 of 30) of these patients had an “unclassified” late effect (depression, postnephrectomy, asplenia, or fibroadenoma in radiation site).
TABLE 6
CTCv2 Grades of Late Effects By Organ System
Category
System affected:
Auditory
Blood/bone marrow
Cardiovascular
Constitutional symptoms
Dermatology
Endocrine
Gastrointestinal
Infection
Musculoskeletal
Neurology
Pain
Renal
Second malignancy
Sexual/reproductive
Coded only in late radiation
morbidity scoring
Total no. of late effects
No.
Grade 1
Grade 2
Grade 3/4
2
1
20
4
6
12
2
21
23
6
3
3
3
7
0
0
8
1
3
4
2
10
8
2
1
2
0
1
0
0
9
3
3
7
0
7
2
2
2
1
0
0
2
1
3
0
0
1
0
4
13
2
0
0
3
6
2
115
0
42
0
36
2
37
CTCv2: Common Toxicity Criteria version 2.
patients had Grade 3 or 4 late effects that could be
considered as nonlife-threatening sequelae that have
a significant long term physiologic or psychologic burden. Categories of late effects included in this group
were: Auditory (bilateral hearing loss requiring hearing aid); Cardiovascular (hypertension); Musculoskeletal (above-the-knee amputation, limb salvage, severe
facial deformity after irradiation requiring plastic surgery, severe scoliosis with Harrington rod placement,
and chronic pain); Neurology (profound cognitive
dysfunction); Other Late Radiation Morbidity (recurrent small bowel obstruction, vaginal stenosis); and
Sexual/Reproductive Function (infertility, ovarian failure, testicular atrophy).
Of the 27 patients who were exposed to a cumulative dose of an anthracycline ⱖ 300 mg/m2, 13 patients (48%) had evidence of altered left ventricular
function. Six survivors had Grade 1 changes (see Table
3 for grading criteria) whereas seven had Grade 2
changes. The mean cumulative anthracycline dose,
age at treatment, and interval since treatment was not
statistically different for survivors with and without
left ventricular dysfunction. An additional three patients were diagnosed with Grade 2 left ventricular
dysfunction who received mantle radiation only (two
patients) or mantle radiation in combination with an
anthracycline (one patient).
Eighteen patients were hepatitis C antibody positive, including 6 patients with persistently (ⱖ 6
months) elevated alanine aminotransferase levels
ⱖ 1.5 times normal, 3 patients with evidence of early
cirrhosis who were treated with interferon-␣, and 1
patient with advanced cirrhosis.
DISCUSSION
As childhood cancer survivors enter adulthood, new
questions arise regarding their long term health care.
Should the adult survivor be followed in a pediatric
institution? What role will primary care physicians
play in the health care of this population? Rosen emphasizes that young adult survivors need health care
provided by adult-oriented physicians.8 Although
transition programs have been suggested as a potential method of long term follow-up of young adult
survivors, to our knowledge little has been written
regarding the structure and health care provided by
such a program.7-11 The current study presents an
example of an interdisciplinary transition program
based in an adult-oriented ambulatory care setting
that links the expertise of the pediatric oncology team,
family physicians, and a network of pediatric and
adult subspecialists.
Late effects commonly are diagnosed in young
adult survivors of childhood cancer who are followed
longitudinally. Approximately 69% of the patients reported in the current study had at least one late effect
of their cancer therapy. Late effects varied in severity,
with nearly one-third of all patients having moderate
to severe late effects. Musculoskeletal abnormalities,
left ventricular dysfunction, hepatitis C, and hypothyroidism were the most common late effects seen in
this population of young adult survivors. The prevalence of left ventricular dysfunction seen in this population was similar to that reported in other follow-up
studies.18-20 Similarly, 32% of the ALL survivors followed in the ACE Young Adult Program were positive
for the hepatitis C virus, which is within the 23– 49%
range of prevalence reported in longitudinal studies.21-23
The findings of the current study are similar to
those noted in populations of childhood cancer survi-
Young Adult Survivors of Childhood Cancer/Oeffinger et al.
1693
TABLE 7
Late Effects Diagnosed in Adolescent and Young Adult Survivors of Childhood Cancer in Four Single Institution Studies
Category
No. of patients
Setting
Median age, current age (yrs)
Median interval (yrs)
Late effects, % of patients
ⱖ2 late effects, % of patients
Grading system
Late effect Grade ⱖ3, % of
patients
Primary cancer types
ALL
Hodgkin disease
NHL
Sarcomas
Wilms’ tumor
Neuroblastoma
CNS tumor
Other
Garré et al.12
Italy, 1994
von der Weid et al.13
Switzerland, 1996
Stevens et al.24
U.K., 1998
Oeffinger et al. U.S., 1999
(current study)
288
Children’s Hospital
15
8
69%
49%
Institution specific
30
Children’s Hospital
15
NR
67%
NR
SPOG
290
Children’s Hospital
23
14
58%
32%
None used
96
Adult setting
23
15
69%
36%
CTCv2
25%
NR
NR
30%
20%
15%
9%
11%
13%
10%
6%
16%
37%
10%
17%
10%
10%
6%
4%
6%
36%
15%
NR
NR
11%
NR
11%
27%
29%
15%
12%
24%
9%
3%
1%
7%
NR: not reported; SPOG: Switzerland Pediatric Oncology Group; CTCv2: Common Toxicity Criteria version 2; ALL: acute lymphocytic leukemia; NHL: non-Hodgkin lymphoma; CNS: central nervous system.
vors seen in long term follow-up clinics in three other
studies (Table 7).12,13,24 With the exception of CNS
tumors, the cancer groups seen in the patient population in the current study are similar to those reported in these three studies. The percent of childhood cancer survivors with a late effect diagnosed in
long term follow-up has been reported to range from
58 –71% in these studies. Multiple late effects are common, occurring in approximately 32– 49% of patients.
The Swiss Pediatric Oncology Group (SPOG) study
reported that 43% (13 of 30) of their patients were
diagnosed with a late effect that previously was undetected and required therapy or closer surveillance.13
Similarly, we reported that 24% of patients in the
current study had an asymptomatic late effect of
CTCv2 Grade 2– 4 (identified by us for the first time)
that necessitated treatment or close follow-up and/or
further evaluation. The data from the current study
also add to the findings of Garré et al.12 that a significant portion of childhood cancer survivors have moderate to severe late effects that require long term treatment, affect their daily activities, or require continued
close surveillance.
Grading of late effects can provide useful information for comparing treatment and long term follow-up
strategies. The current report adds to the findings of
two other studies in the use of a grading system for
late effects.12,13 To our knowledge, as yet there is no
universally accepted grading system that has been
developed and validated solely for the study of late
effects related to all treatment modalities. Garré et al.
developed a set of criteria to grade late effects, with
toxicity grades including: Grade 0: no late effect; Grade
1: asymptomatic changes that did not require any
corrective measure and did not influence the subject’s
general activity; Grade 2: moderate symptomatic
changes interfering with the subject’s activity; Grade
3: severe symptomatic changes that required major
corrective measures and strict and prolonged surveillance; and Grade 4: life-threatening sequelae.12 SPOG
developed a grading system for late effects in childhood cancer survivors and piloted its use in 30 patients, half of whom were age ⬎ 16 years.13 However,
to our knowledge validation studies of the SPOG grading system have not been published. The SPOG system
also ranges from 0 to 4, with Grade 0: no late effect;
Grade 1: asymptomatic patient requiring no therapy;
Grade 2: asymptomatic patient, requires continuous
therapy or continuous medical follow-up or symptomatic late effects resulting in reduced school, job, or
psychosocial adjustment while remaining fully independent; Grade 3: physical or mental sequelae not
likely to be improved by therapy but able to work at
least partially; and Grade 4: severely handicapped patients unable to work independently.
In general, the CTCv2 guidelines are similar to the
grading systems described earlier. However, the
CTCv2 grading scheme is more detailed, including
criteria specific for the majority of organ systems affected. These organ specific criteria should reduce the
1694
CANCER April 1, 2000 / Volume 88 / Number 7
interrater variability, although further validation in the
long term cancer survivor population is needed to
render it more applicable to the late effects setting.
The only two categories in which the “Other” category
was repeatedly used in our study were “Musculoskeletal” and “Infection,” and the grading scheme was
modified as discussed earlier. Otherwise, late effects
were graded easily with the CTCv2.
An additional finding that is important to note is
the underrepresentation of minorities who have been
seen in the ACE Young Adult Program. African-American and Hispanic patients comprised 33% of the children newly diagnosed with cancer at the Children’s
Medical Center of Dallas between 1993–1997, whereas
thus far they have comprised only 14% of the patients
seen in the ACE Young Adult Program. This is similar
to the findings of the National Wilms’ Tumor Study
Group, which reported a 10-year cumulative loss to
follow-up of 45.5% for African-American survivors and
36.5% for Hispanic survivors compared with 21.5% for
white, non-Hispanic survivors.25 To understand better
the potential barriers to long term follow-up faced by
underrepresented or underserved minorities, the investigators of the ACE Young Adult Program currently
are analyzing data of a retrospective cohort of childhood cancer patients diagnosed between 1990 –1995
at Children’s Medical Center of Dallas. Socioeconomic, cancer-related, and gender-/age-related factors that might predict loss to follow-up are being
evaluated.
Several limitations should be recognized in the
interpretation of the current study. The sample size
was relatively small, limiting analysis between cancer
types or with longitudinal follow-up. Second, the CTC
grades were assigned by means of a retrospective review of the diagnosed late effects. For reasonably valid
comparisons of treatment groups and cancers, a validated grading system used prospectively will be essential. Third, the current study population lacked patients with CNS tumors. Finally, a selection bias is
introduced by the very nature of a long term follow-up
program. Only survivors who decided to come for
evaluation were available for assessment and comparison. This may overrepresent patients with symptomatic late effects who are more likely to be concerned
about their health. However, it should be noted that a
substantial number of patients (24%) who were evaluated were asymptomatic and were diagnosed with a
moderate to severe late effect that was unrecognized
previously.
There is still much that is not understood regarding the health problems of and the delivery of care to
adult survivors of childhood cancer. Research to date
has focused on the late effects during the first 10 –15
years after therapy and now it is necessary to expand
this body of knowledge to the adult years when many
new variables arise. What effect will life-style and risk
behavior, such as smoking, have on the incidence rate
of second primary malignancies? How will previous
therapies, such as mantle radiation, affect the progression of common adult health problems such as coronary artery disease? Perhaps equally important are
outcome studies evaluating the cost-effectiveness of
different screening and surveillance strategies and
secondary prevention interventions. As survivors
move into the adult years, start their careers and families, and move away from their parents and their
treating institutions, more and more will seek their
health care from primary care physicians. How will the
communication between pediatric cancer centers and
primary care physicians be facilitated? Finally, as we
enter this new millennium it is essential that this
growing population of aging childhood cancer survivors be viewed as a high risk, underserved group that
has potential for widely diverse physiologic and psychosocial problems and faces significant impediments
to the access of medical care in our current health care
system.
The current study describes a multidisciplinary
transition program in an ambulatory, adult-based setting for young adult survivors of childhood cancer, a
program that might be viewed as a model for others.
These findings add to the growing knowledge base
that supports the necessity of long term, longitudinal
follow-up of childhood cancer survivors who have
reached adulthood and demonstrate the potential
value of grading of late effects.
REFERENCES
1.
2.
3.
4.
5.
6.
7.
8.
Robison LL. Issues in the consideration of intervention
strategies in long-term survivors of childhood cancer. Cancer 1993;71:3406 –10.
Meadows AT, Gallagher JA, Bunin GR. Late effects of early
childhood cancer therapy. Br J Cancer 1992;66:S92–5.
Green DM. Long term complications of treatment for cancer
during childhood and adolescence. Baltimore: Johns Hopkins University Press, 1989:1–165.
DeLaat CA, Lampkin BC. Long-term survivors of childhood
cancer: evaluation and identification of sequelae of treatment. CA Cancer J Clin 1992;42:263– 82.
Meister LA, Meadows AT. Late effects of childhood cancer
therapy. Curr Probl Pediatr 1993;23:102–24.
Oeffinger KC, Eshelman DA, Tomlinson GE, Buchanan GR.
Programs for adult survivors of childhood cancer. J Clin
Oncol 1998;16:2864 –7.
Bleyer WA, Smith RA, Green DM, DeLaat CA, Lampkin BC,
Coltman CA, et al. Workgroup #1: Long-term care and lifetime follow-up. Cancer 1993;71:2410 –25.
Rosen DS. Transition to adult health care for adolescents
and young adults with cancer. Cancer 1993;71:3411– 4.
Young Adult Survivors of Childhood Cancer/Oeffinger et al.
9.
10.
11.
12.
13.
14.
15.
16.
17.
Konsler GK, Jones GR. Transition issues for survivors of
childhood cancer and their healthcare providers. Cancer
Pract 1993;1:319 –24.
Maclean WE, Foley GV, Ruccione K, Sklar C. Transitions in
the care of adolescent and young adult survivors of childhood cancer. Cancer 1996;78:1340 – 4.
Meadows AT, Black B, Nesbit ME, Strong LC, Nicholson HS,
Green DM, et al. Long-term survival: clinical care, research,
and education. Cancer 1993;71:3213–5.
Garré ML, Gandus S, Cesana B, Haupt R, De Bernardi B,
Comelli A, et al. Health status of long-term survivors after
cancer in childhood. Am J Pediatr Hematol Oncol 1994;16:
143–52.
von der Weid N, Beck D, Caflisch U, Feldges A, Wyss M,
Wagner HP. Standardized assessment of late effects in longterm survivors of childhood cancer in Switzerland: results of
a Swiss Pediatric Oncology Group (SPOG) pilot study. Int
J Pediatr Hematol/Oncol 1996;3:483–90.
RTOG/EORTC. Late effects consensus conference: RTOG/
EORTC. Radiother Oncol 1995;35:5–7.
Rubin P, Constine LS, Fajardo LF, Phillips TL, Wasserman
TH. Overview of late effects normal tissues (LENT) scoring
system. Radiother Oncol 1995;35:9 –10.
Pavy JJ, Denekamp J, Letschert J, Littbrand B, Mornex F,
Bernier J, et al. Late effects toxicity scoring: the SOMA scale.
Radiother Oncol 1995;35:11–5.
National Cancer Institute. Common Toxicity Criteria, version 2. Bethesda, MD: National Cancer Institute, 1998.
1695
18. Lipshultz SE, Lipsitz SR, Mone SM, Goorin AM, Sallan SE,
Sanders SP, et al. Female sex and drug dose as risk factors
for late cardiotoxic effects of doxorubicin therapy for childhood cancer. N Engl J Med 1995;332:1738 – 43.
19. Grenier MA, Lipshultz SE. Epidemiology of anthracycline
cardiotoxicity in children and adults. Semin Oncol 1998;25(4
Suppl 10):72– 85.
20. Giantris A, Abdurrahman L, Hinkle A, Asselin B, Lipshultz
SE. Anthracycline-induced cardiotoxicity in children and
young adults. Crit Rev Oncol Hematol 1998;27:53– 68.
21. Arico M, Maggiore G, Silini E, Bono F, Vigano C, Cerino A, et
al. Hepatitis C virus infection in children treated for acute
lymphoblastic leukemia. Blood 1994;84:2919 –22.
22. Dibenedetto SP, Ragusa R, Sciacca A, Di Cataldo A, Miraglia
V, D’Amico S, et al. Incidence and morbidity of infection by
hepatitis C virus in children with acute lymphoblastic leukaemia. Eur J Pediatr 1994;153:271–5.
23. Locasciulli A, Testa M, Pontisso P, Benvegnu L, Fraschini D,
Corbetta A, et al. Prevalence and natural history of hepatitis
C infection in patients cured of childhood leukemia. Blood
1997;90:4628 –33.
24. Stevens MCG, Mahler H, Parkes S. The health status of adult
survivors of cancer in childhood. Eur J Cancer
1998;34:694 – 8.
25. Breslow N, Olshan A, Beckwith B, Moksness J, Feigl P, Green
D. Ethnic variation in the incidence, diagnosis, prognosis
and follow-up of children with Wilms tumor. J Natl Cancer
Inst 1994;86:49 –51.
Документ
Категория
Без категории
Просмотров
7
Размер файла
87 Кб
Теги
313
1/--страниц
Пожаловаться на содержимое документа