close

Вход

Забыли?

вход по аккаунту

?

Report of a panel on the relationship between public exposure to pesticides and cancer

код для вставкиСкачать
2005
Hyperbaric Oxygen Therapy for Radiation-Induced
Brain Injury in Children
Paul J. Chuba, M.D., Ph.D.1
Patricia Aronin, M.D.2
Kanta Bhambhani, M.D.3
Michael Eichenhorn, M.D.4
Lucia Zamarano, M.D.2
Paul Cianci, M.D.5
Michael Muhlbauer, M.D.6
Arthur T. Porter, M.D.1
James Fontanesi, M.D.1
BACKGROUND. Radiation-induced necrosis (RIN) of the brain is a complication
associated with the use of aggressive focal treatments such as radioactive implants
and stereotactic radiosurgery. In an attempt to treat patients with central nervous
system (CNS) RIN, ten patients received hyperbaric oxygen treatment (HBOT).
METHODS. Patients presented with new or increasing neurologic deficits associated
1
Department of Radiation Oncology, Karmanos
Cancer Institute, Wayne State University, Detroit, Michigan.
2
Department of Neurosurgery, Karmanos Cancer Institute, Wayne State University, Detroit,
Michigan.
3
Department of Pediatric Oncology, Karmanos
Cancer Institute, Wayne State University, Detroit, Michigan.
4
Department of Hyperbaric Medicine, Henry
Ford Hospital, Detroit, Michigan.
with imaging changes after radiotherapy. Necrosis was proven by biopsy in eight
cases. HBOT was comprised of 20–30 sessions at 2.0 to 2.4 atmospheres, for 90
minutes-2 hours. Sites of RIN included the brain stem (n Å 2), posterior fossa (n
Å 1), and supratentorial fossa (n Å 7). Histologic types included brain stem glioma
(n Å 2), ependymoma (n Å 2), germinoma (n Å 2), low grade astrocytoma (n Å
1), oligodendroglioma (n Å 1), glioblastoma multiforme (n Å 1), and arteriovenous
malformation (n Å 1).
RESULTS. Initial improvement or stabilization of symptoms and/or imaging findings were documented in all ten patients studied and no severe HBOT toxicity
was observed. Four patients died, with the cause of death attributed to tumor
progression. Five of six surviving patients were improved by clinical and imaging
criteria; one patient was alive with tumor present at last follow-up.
CONCLUSIONS. HBOT may prove to be an important adjunct to surgery and steroid
therapy for CNS RIN. Cancer 1997;80:2005–12. q 1997 American Cancer Society.
KEYWORDS: radiation-induced necrosis, hyperbaric oxygen therapy, children, stereotactic radiosurgery, central nervous system.
5
Department of Hyperbaric Oxygen Therapy,
Brookside Medical Center, San Pablo, California.
6
Department of Neurosurgery, St. Jude Children’s Research Hospital, Memphis, Tennessee.
Presented in part at the Fourth International
Conference on Long-Term Complications of
Treatment of Children and Adolescents for Cancer, Buffalo, New York, June 14–15, 1996.
Address for reprints: Paul J. Chuba, M.D.,
Ph.D., Department of Radiation Oncology,
Harper Hospital/Karmanos Cancer Institute,
3990 John R, Detroit, MI 48236.
Received February 27, 1997; revision received
June 3, 1997; accepted June 3, 1997.
R
adiation-induced necrosis (RIN) of the brain ranks among the
most debilitating sequelae of therapeutic radiation of the central
nervous system.1,2 In the authors’ experience the incidence of symptomatic RIN in children may be increasing with the use of more
aggressive local therapies such as radioactive implants and stereotactic radiosurgery (SRS), especially when combined with chemotherapy.
Classic treatment for patients with RIN has been to attempt to control
cerebral edema with steroids and then to resect avascular necrotic
debris.2 Other treatments have been investigated including nonsteroidal antiinflammatory drugs, anticoagulants,3 and lipid peroxidase inhibitors.4 One promising new therapeutic intervention is hyperbaric
oxygen treatment (HBOT), or the intermittent inhalation of 100% oxygen under high pressure.5,6 When used after radiation injury, HBOT
has been shown to increase tissue oxygen concentration, thereby
stimulating angiogenesis and establishing a new capillary blood supply.7,8 HBOT has proven effectiveness in the management of RIN in
other sites.9 – 10 In this report the authors describe its use in ten patients
diagnosed with focal RIN of the brain.
PATIENTS AND METHODS
Between 1990 and 1994, ten patients diagnosed with RIN of the central
nervous system (CNS) were treated with HBOT at three different cen-
q 1997 American Cancer Society
/ 7b8a$$1414
10-21-97 14:46:33
canal
W: Cancer
2006
CANCER November 15, 1997 / Volume 80 / Number 10
TABLE 1
Patient Characteristics and Summary of Previous Treatment
No.
Age
(yrs)
Gender
Race
Histology
Location
EBRT
Dosea
DPFb
SRS
doseb
Implant
dosed
Chemotherapy e
1
2
3
4
5
6
7
8
9
10
10
5
14
12
9
14
4
12
13
23
F
F
M
M
F
M
M
M
F
F
AA
AA
W
W
W
AA
W
W
W
W
Glioma, Grade 2
Glioma, Grade 1
Ependymoma
Germinoma
Ependymoma
Mixed germ cell
Glioblastoma
Oligodendroglioma
Pilocytic astroc.
AVM
Pontine
Pontine
Occipital
Suprasellar
4th ventricle
Pineal
Frontal
Parietal-occipital
Thalamic
Supratent.
7020
5400
5580
5040
6960
4560
7040
2400, 5040
5400
0
117
180
180
180
120
120
110
150
180
—
0
0
1500
0
1500
800
0
0
0
1700
0
0
0
0
0
0
6000
5000
20,000
0
A
A
B
C
None
C
None
D
None
None
EBRT: external beam radiation therapy; DPF: dose per fraction; SRS: stereotactic radiosurgery; F: female; M: male; AA: African American; W: white; astroc: astrocytoma; AVM: arteriovenous malformation; supratent:
supratentorial.
a
All doses are given in centigrays (cGy). Patient 8 underwent craniospinal irradiation for acute lymphoblastic leukemia 8 years prior to being diagnosed with a primary brain tumor, then had 5040 cGy external
beam plus implant.
b
Dose per fraction of °120 cGy were delivered on a twice-daily basis.
c
Patients 3 and 5 were treated with stereotactic radiosurgery at recurrence. Patient 10 was treated using 17 grays to 2 overlapping isocenters.
d
Patient 9 received injection of 1850 microcuries 32P into cyst. Other implants were permanent 125I seed implants.
e
Chemotherapy regimens were as follows: Regimen A was concurrent cisplatinum given as part of Pediatric Oncology Group protocol 9373; regimen B was mechlorethamine, vincristine, procarbazine, and
prednisone) given as adjuvant for 1 year after the initial external beam radiation therapy. Regimen C was comprised of five drugs (cyclophosphamide, vincristine, bleomycin, etoposide, and cisplatin) for six cycles
given before (Patient 4), or after (Patient 6) external beam radiation therapy; Regimen D was comprised of feniposide and cytarabine.
ters. HBOT was comprised of a minimum of 20 treatment sessions at 2.0 – 2.4 atmospheres (atm) with inhalation of 100% oxygen, for 90 minutes-2 hours.
Multiplace hyperbaric chambers were used so that a
companion could be assigned to accompany children
when necessary. These individuals were monitored by
a chamber monitor during treatment. Because HBOT
may lower the seizure threshold, intravenous access
was maintained in patients with a history of recent
seizure. Standard exclusionary rules such as pneumocephalus and bleb formation were followed. Patients
and their families were provided with educational brochures and informed consent was obtained.
Patient characteristics and CNS therapeutic treatments prior to HBOT are summarized in Table 1. All
patients had received external beam radiation therapy
to the brain with dose per fraction ranging from 117 –
180 centigrays (Table 1). Four patients were treated
according to twice-daily radiation protocols. Radiation
doses for fractionated external beam radiation ranged
from 24 – 70.4 grays (Gy). Three patients received boost
irradiation with 125I interstitial implant with total implant doses of 60 Gy in each. Three patients received
single fraction SRS with doses of 8 Gy, 15 Gy, and 17
Gy, respectively. Six patients had chemotherapy either
before, concomitant with, or after radiation therapy.
Patient age at the start of HBOT ranged from 4 –
23 years, and included 5 females and 5 males, 3 of
whom were African American, and 7 of whom were
white. Sites of RIN included the brain stem (two pa-
/ 7b8a$$1414
10-21-97 14:46:33
tients), and posterior fossa (one patient), with the remainder being supratentorial. Initial tumor histologies
included brain stem glioma (two patients), ependymoma (two patients), germinoma (two patients), low
grade astrocytoma (one patient), oligodendroglioma
(one patient), and glioblastoma multiforme (one patient). One patient with an arteriovenous malformation (AVM) was treated. All patients presented with
new or increasing neurologic deficits associated with
imaging changes. Similarly, all patients had clinically
failed steroid therapy prior to the initiation of HBOT.
For evaluation of patient response to HBOT, symptoms and imaging findings (including enhancement,
edema, and mass effect) attributed to RIN were scored
as improved, worsened, or stabilized.
RESULTS
The presenting symptoms and the course of resolution
or progression of both symptoms and imaging findings
for ten patients treated with HBOT are shown in Table
2. For two patients, the diagnosis of RIN was made
only on a radiologic basis (i.e., no biopsy was performed). For the remaining eight patients, biopsy
proved the presence of RIN; in two of these patients
RIN was found together with the pathologic diagnosis
of persistent tumor. Magnetic resonance imaging
(MRI) findings characterized by enhancement, mass
effect, or focally increased proton density and increased T2 signal that were consistent with RIN. The
latent period between the completion of radiation
canal
W: Cancer
Hyperbaric Oxygen for RIN/Chuba et al.
2007
TABLE 2
Patient Outcome With HBOT
No.
Biopsy
Latent
period (mos)
Symptoms
No. of
HBOT
Symptoms
Imaging
F/Ua
Status
1
2
3
4
5
6
7
8
9
10
Necrosis
None
Necrosis with tumor
Necrosis
Necrosis
Necrosis
None
Necrosis
Necrosis with tumor
Necrosis
8
14
5
7
4
10
12
5
2
9
Inc ataxia, CN palsies
Inc CN palsies
Headache and dysphasia
Headache and ataxia
Ataxia
Hemiparesis
Headache
Headache and seizures
Left-sided visual loss
Motor Weakness
30
30
35
40
30
25
20
20
20
30
Stabilized initially
Stabilized initially
Improved
Improved
Stabilized
Improved
Resolved
Improved initially
Improved
Improved initially
Stabilized initially
Worsened
Stabilized
Improved
Stabilized
Improved
Stabilized
Improved initially
Improved
Improved initially
7
6
3
12
9
7
8
3
10
36
Died
Died
Alive with tumor
Alive, NED
Died
Alive, NED
Alive, NED
Alive
Died
Alive
HBOT: hyperbaric oxygen treatment; F/U: follow-up; CN: cranial nerve; inc: increasing; NED: no evidence of disease.
a
Months of follow-up from the date of completion of hyperbaric oxygen treatment is stated.
therapy and the diagnosis of RIN ranged from 2 – 14
months. The most common symptom associated with
RIN was increasing headache (four patients), followed
by increasing ataxia (three patients), new onset cranial
nerve palsy (two patients), seizures (one patient), or
visual loss (one patient). No severe HBOT toxicity was
observed. One patient developed ear pain and required placement of myringotomy tubes. For one child
the HBOT treatments were discontinued after sinusitis
developed.
Initial improvement or stabilization of symptoms
was documented in all ten patients studied (Table 1).
In addition, for nine of the ten patients, initial stabilization or improvement of imaging findings also was
observed. At the time of analysis, four patients had
died, one patient was alive with tumor present, and
five patients were alive without evidence of disease.
Follow-up from the time of initial diagnosis ranged
from 6 – 38 months (median, 21 months) and followup from the time of initiation of HBOT ranged from
3 – 36 months (median, 7 months). The median followup for surviving patients was 19 months.
In the patients who died, the cause of death was
attributed to tumor progression in all four cases. Transient improvement was noted in one child with a brain
stem glioma (Patient 1; both the MRI and symptoms
were stable for 4 months), who subsequently died 7
months after HBOT. Autopsy confirmed progressive
tumor. A second child, also with a brain stem glioma
(Patient 2), had initial stabilization of symptoms for
3 months after HBOT although the T2-weighted MRI
abnormality appeared to worsen. This patient also
died with tumor progression. Patient 5 (treated with
SRS at biopsy proven recurrence of ependymoma) required reoperation for mass effect 20 months after
HBOT; only nonnecrotic debris was found. However,
this patient subsequently died with progressive dis-
/ 7b8a$$1414
10-21-97 14:46:33
ease. Patient 9 demonstrated quantitative improvement in visual acuity for 5 months before death (from
20/200 to 20/60 in the right eye and from hand motion
to finger counting ability in the left eye) despite radiographic evidence of progressive tumor.11
For the six patients still alive at follow-up, stabilization and/or improvement of symptoms and imaging
findings appeared to be durable. The patients had presented with symptoms of headache, dysphasia, ataxia,
and visual loss, but not with cranial nerve palsies or
seizures (Table 2). Patient 6 developed RIN 5 months
after treatment with surgery, chemotherapy, and radiation therapy for a pineal germinoma (Figs. 1a and
1b). Five months after completion of radiation, he developed left hemiparesis and the MRI showed a new
lesion in the right periventricular white matter (Figs.
1c and 1d). Corticosteroid therapy was initiated and a
stereotactic biopsy demonstrated RIN without tumor.
He then underwent 25 HBOT sessions with complete
resolution of symptoms. Seven months later the T2weighted MRI abnormality remained improved (Figs.
1e and 1f ). Patient 4 developed RIN after surgery, chemotherapy, and radiation therapy for suprasellar germinoma (Figs. 2a and 2b). Seven months after treatment he developed severe ataxia and characteristic
imaging changes (Figs. 2c and 2d). Cerebellar RIN was
diagnosed on biopsy. Five months after HBOT, improvement in both clinical symptoms and imaging was
noted (Figs. 2e and 2f ).
Outcomes for the four other surviving patients
were as follows. Patient 8 (patient with oligodendroglioma treated with a radioactive implant) had transient
resolution of symptoms (seizures and headaches) beginning midway through the HBOT but required reoperation within 3 months. Patient 10 (treated with linac
SRS for AVM; 17 Gy to 2 overlapping isocenters), who
developed RIN after 10 months and initially improved
canal
W: Cancer
2008
CANCER November 15, 1997 / Volume 80 / Number 10
FIGURE 1. Serial magnetic resonance imaging findings in a 14-year-old male treated with surgery, radiation, and chemotherapy for pineal germinoma.
The patient initially had a shunt placed and underwent stereotactic surgical resection with gross total removal. (a) T1-weighted, gadolinium-enhanced
coronal and (b) proton density axial images performed after surgery but prior to treatment with chemotherapy and radiation are shown. Five months
after completing 4 cycles of chemotherapy and local field hyperfractionated radiation (45 grays [Gy]) and single fraction stereotactic radiosurgery
boost (8 Gy), he returned with a new onset left hemiparesis with imaging showing a new lesion enhancing in the right periventricular white matter
with edema, mass effect, and midline shift on (c) coronal T1-weighted, gadolinium-enhanced and (d) axial proton density images. Focal radiationinduced necrosis without tumor was demonstrated on biopsy. Repeat imaging was performed 7 months after completing hyperbaric oxygen treatment
with (e) coronal T1-weighted, gadolinium-enhanced and (f) axial proton density studies showing near complete resolution of the abnormality.
with HBOT, later required reoperation for edema with
mass effect. Patient 3 (treated with SRS at biopsy
proven recurrence of intracranial ependymoma) remained alive with tumor present. and Patient 7
(treated with external beam radiation therapy and radioactive implant for glioblastoma multiforme) remained without evidence of disease and had stable
MRI findings 9 months after completion of HBOT.
DISCUSSION
Well established indications for HBOT include decompression sickness, air embolism, carbon monoxide poisoning, and RIN in various sites.5,9 Serious complications
are rare but may include oxygen toxicity (not found with
short duration and relatively low pressure), and closed
cavity barometric pressure trauma. In this study the authors described the use of HBOT in the treatment of ten
patients diagnosed with RIN of the CNS.
/ 7b8a$$1414
10-21-97 14:46:33
RIN of the CNS may be divided into focal necrosis, which usually is found at the site of the tumor,
and diffuse white matter injury.1 – 3 Both are believed to result from increased tissue pressure from
edema, vascular injury leading to infarction, damage to endothelial cells, and fibrinoid necrosis of
small arteries and arterioles. Damage to oligodendroglial supporting cells with demyelination, reactive gliosis, and coagulation necrosis also may occur.1,2 Diffuse white matter injury usually follows
large volume or whole brain irradiation and may
lead to cerebral atrophy although the course of progression is usually protracted. Focal RIN, when severe, is a highly debilitating condition leading to
mass effect.3 Symptoms may include personality
change, confusion, memory impairment, learning
difficulties, dementia, seizure disorder, and motor
abnormalities. The angiogram is avascular and the
canal
W: Cancer
Hyperbaric Oxygen for RIN/Chuba et al.
FIGURE 1. (continued)
/ 7b8a$$1414
10-21-97 14:46:33
canal
W: Cancer
2009
2010
CANCER November 15, 1997 / Volume 80 / Number 10
FIGURE 2. Serial magnetic resonance imaging (MRI)findings in a 12-year-old male treated with surgery, radiation, and chemotherapy for a mixed
germ cell tumor in the suprasellar region. His past medical history was significant for total resection of a mature teratoma from the pineal area 3
years previously. (a) Axial T1-weighted, gadolinium-enhanced and axial T2 images performed after surgery show mild edema in the posterior aspect
of the cerebellum. Five months after completion of radiation he developed radiation-induced necrosis (RIN) with severe ataxia and characteristic
imaging changes (enhancement and edema) on (c) axial and (d) sagittal T1-weighted, gadolinium-enhanced MRI. Cerebellar RIN was diagnosed on
biopsy. Five months after hyperbaric oxygen treatment, improvement in both clinical symptoms and the axial (e) T1-weighted, gadolinium-enhanced,
and sagittal (f) MRIs are shown.
computed tomography volume enhances due to
breakdown of the blood-brain barrier. Focal RIN
appears to be increasing with the use of implants
and SRS.
The patients presented in the current study
were a highly select group and represented only
those undergoing HBOT; therefore no definite conclusions may be drawn regarding the incidence and
prevalence of RIN or predictive factors. Nonetheless, a very high proportion of patients were treated
with surgery, chemotherapy, and high dose radiation with focal techniques. Nine of ten patients
were age ° 14 years. Stable or improved symptoms
were noted initially for all patients (Table 2) and
stable or improved imaging studies also were noted
initially for nine of ten patients. For six surviving
patients these findings appeared to be durable at
3 – 36 months of follow-up. Four patients died with
/ 7b8a$$1414
10-21-97 14:46:33
progressive symptoms attributed to tumor progression. Autopsy on one of the patients who died
showed persistent tumor. In one patient HBOT was
stopped because of sinusitis, and one patient underwent placement of myringotomy tubes secondary to ear pain.
Although HBOT may prove to be an important
adjunct to steroid therapy and surgery for RIN in
children and adults it is expensive, and the data
presented in this study have several limitations.
Two of the patients described herein did not undergo biopsy. Also, because of the small number of
patients, the authors were unable to examine which
pretreatment factors predict for a response to
HBOT and cannot assess any possible effect of
HBOT on tumor progression. More important, the
authors were unable to determine the relative effects of steroid therapy in combination with HBOT
canal
W: Cancer
Hyperbaric Oxygen for RIN/Chuba et al.
2011
FIGURE 2. (continued)
on these patient’s outcomes because patients received standard steroid therapy before, during, and
after HBOT. This is likely to continue to be a drawback in future studies. Nonetheless, in a group with
few treatment options available, HBOT was well tol-
/ 7b8a$$1414
10-21-97 14:46:33
erated and most patients improved both symptomatically and by imaging criteria. Further follow-up
and collection of multiinstitutional data are needed
to determine the generalizing ability of these observations.
canal
W: Cancer
2012
CANCER November 15, 1997 / Volume 80 / Number 10
6.
REFERENCES
1.
2.
3.
4.
5.
Sheline GE, Wara WM, Smith V. Therapeutic irradiation and
brain injury. Int J Radiat Oncol Biol Phys 1980;6:1215–28.
Gutin PH. Treatment of radiation necrosis of the brain. In:
Gilbert JA, Kagan AR, editors. Radiation damage to the nervous system. New York: Raven Press, 1980:155.
Glantz MJ, Burger PC, Friedman AH, Radtke RA, Massey EW,
Schold SC. Treatment of radiation -induced nervous system
injury with heparin and warfarin. Neurology 1994;44:2020–
7.
Buatti JM, Friedman WA, Theele DP, Bova FJ, Mendenhall
WM. The lazaroid U74389G protects normal brain from stereotactic radiosurgery-induced radiation injury. Int J Radiat
Oncol Biol Phys 1996;34:591–7.
Sanchez EC, Myers AM. Hyperbaric oxygen therapy in the
pediatric patient. A 20-year experience [abstract]. Undersea
Biomed Res Suppl 1992;19:109.
/ 7b8a$$1414
10-21-97 14:46:33
Ashamalla HL, Thom SR, Goldwein JW. Hyperbaric oxygen
therapy for the treatment of radiation-induced sequelae in
children. Cancer 1996;77:2407–12.
7. Knighton DR, Hunt TK, Schenestuhl H, et al. Oxygen tension
regulates the expression of angiogenesis factor by macrophages. Science 1983;221:1283–9.
8. Marx RE Ehler WJ, Tayapongsak PT, Pierce LW. Relationship
of oxygen dose to angiogenesis induction in irradiated tissue. Am J Surg 1990;160:519–24.
9. Marx RE, Johnson RP, Kline SN. Prevention of osteoradionecrosis: a randomized prospective clinical trial of hyperbaric
oxygen versus penicillin. J Am Dent Assoc 1985;111:49–54.
10. Hart GB, Mainous EG. The treatment of radiation necrosis
with hyperbaric oxygen. Cancer 1976;37:2850–5.
11. Fontanesi J, Golden EB, Cianci PC, Heideman RL. Treatment
of radiation-induced optic neuropathy in the pediatric population. J Hyperbar Med 1991;6:245–8.
canal
W: Cancer
Документ
Категория
Без категории
Просмотров
4
Размер файла
476 Кб
Теги
report, cancer, exposure, panel, pesticide, publik, relationships
1/--страниц
Пожаловаться на содержимое документа