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Results: The overall survival rate at 5, 10, and 20 years was 100%, 75%, and 60%, respectively. The progression-freesurvival rate at 5, 10, and 20 years was 93%, 80%, and 60%, respectively. Neither overall survival nor progression-

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Int. J. Radiation Oncology Biol. Phys., Vol. 63, No. 1, pp. 91100, 2005Copyright 2005 Elsevier Inc.free survival was clearly correlated with any patient, tumor, or treatment factors. Neurologic function and KPSworsened after surgery in 8 (57%) of 14 and 9 (69%) of 13 patients, respectively. At a mean follow-up of 10.2 years,neurologic function had stabilized or improved in 8 (73%) of 11 remaining patients, but the KPS had worsened in 5(50%) of 10. Most patients who were employed before surgery were working at last follow-up.Conclusion: Patients who undergo gross total resection of their tumor may be followed closely. Patients who undergolimited resection should continue to receive postoperative RT (50.4 Gy in 1.8-Gy fractions). The functional measuresshould be routinely evaluated to appreciate the treatment outcomes. 2005 Elsevier Inc.

Astrocytoma, Surgery, Radiotherapy, Spinal cord.

INTRODUCTION

mors arising from the spinal canal are rare. Such tumors willount for only 15% of the approximately 18,400 primarytral nervous system tumors diagnosed in 2004 (1). Of the

mary spinal tumors, roughly one-third are intramedullary,th 85% of these having a glial origin in adults (2). In a recenthology review by Miller (3), astrocytomas of the spinal cordre the most common spinal cord tumor in children (39%)

the second most common in adults (24%). Most astrocy-as are low grade, with 25% of adult cases and 10% ofiatric cases demonstrating malignant histologic features (4,Low-grade astrocytoma of the spinal cord (LGASC) affectsles slightly more than females and may occur at any age,hough the tumor tends to present in the first 30 years of life6).

No consensus has been reached in the literature regardingoptimal treatment for LGASC. Series from the past twoades reporting on the results of conservative surgery andiotherapy (RT) for LGASC have demonstrated overall 5-

and 10-year survival rates in the range of 5891% and 4391%, respectively (627). One recent single-institution seriesreported a 5-year overall survival rate of 100% in patientstreated with extensive tumor resection and no postoperativeRT, with a low incidence of morbidity (17). Still, the predom-inant form of failure is local, with failure rates ranging from14% to 52% (7, 9, 14).

In addition to looking at measures of survival, many authorshave also recognized the importance of analyzing functionalmeasures, such as neurologic function and Karnofsky perfor-mance status (KPS), with most relying on one or the other (7,8, 1014, 17, 19, 21, 25, 2831). These measures are partic-ularly important in the case of a tumor whose natural history isso prolonged and for which treatment has many recognizedpotential long-term sequelae. Historically, at least one-half ofthe patients can expect to maintain their baseline functionalstatus, with the remainder equally likely to improve or worsen(8, 1014, 17, 19, 21, 25, 2831).

This review was of our own series of 14 patients with

eprint requests to: John H. Suh, M.D., Department of Radia- 444-5331; E-mail: suhj@ccf.orgdoi:10.1016/j.ijr

INICAL INVESTIGATION

LONG-TERM SURVIVAL AND FUNCTLOW-GRADE ASTROCYT

CLIFFORD G. ROBINSON, M.D.,* RICHARD AIAIN H. KALFAS, M.D., MELVIN D. WHIT

AND JOHN H.Departments of *Radiation Oncology, Anatomic P

Cleveland Clinic Foun

Purpose: To determine survival and changes in neurologseries of patients treated for low-grade astrocytoma of thMethods: This study consisted of 14 patients with patholowho were treated between 1980 and 2003. All patients und 7), subtotal resection (n 6), or gross total resection (n(median total dose 50 Gy in 28 fractions). The overall surfunction and KPS were measured.n Oncology, Cleveland Clinic Foundation, T28, 9500 Euclide., Cleveland, OH 44195. Tel: (216) 444-5574; Fax: (216)

RAc

9105.01.009

Central Nervous System

AL STATUS OF PATIENTS WITHA OF SPINAL CORD

YSON, M.D., JOSEPH F. HAHN, M.D.,, M.D., SHIH-YUAN LEE, M.S.P.H.,*, M.D.*y, and Neurosurgery, Brain Tumor Institute,Cleveland, Ohio

tion and Karnofsky performance status (KPS) in al cord during the past two decades.confirmed low-grade astrocytoma of the spinal cordt decompressive laminectomy followed by biopsy (nTen patients underwent postoperative radiotherapy

progression-free survival, and changes in neurologic

Printed in the USA. All rights reserved0360-3016/05/$see front mattereceived Nov 16, 2004, and in revised form Jan 8, 2005.cepted for publication Jan 11, 2005.

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92 I. J. Radiation Oncology Biology Physics Volume 63, Number 1, 2005ASC, treated predominantly with conservative surgeryd postoperative RT, with special consideration given toeful long-term follow-up of neurologic function andS. This series differed from most in that we included

ly those patients with pathologically confirmed low-graderocytoma.

METHODS AND MATERIALS

tient populationhe institutional review boardapproved low-grade glioma da-

ase at the Cleveland Clinic Foundation Brain Tumor Institutes searched to identify all patients with LGASC treated betweencember 1980 and January 2003. To be included in this study,patients must have been followed for at least 1 year from thee of treatment. In total, 21 patients were identified who hadn treated at our institution. On additional review of the recordsrepeated review of the pathologic materials, 3 patients were

nd to have high-grade tumors and 4 did not have at least 1 yearfollow-up. Of the 4 patients with insufficient follow-up, 1 diedtoperatively of gram-negative sepsis after undergoing gross

al resection (GTR). The records of the remaining 14 patientsre retrospectively reviewed, and the information was enteredo a secure database. The identifying data was removed accord-

to Health Insurance Portability and Accountability ActIPAA) protocols. Information was collected on patient age,der, tumor grade, symptoms at diagnosis, symptom duration,

aging type, disease location and extent, surgery technique, RThnique, failure site, repeat operations, and neurologic function

KPS at each treatment and subsequent follow-up examination.ble 1). Additionally, any complications arising from the med-l treatment, surgery, or RT of the patient were recorded.

sessment of neurologic function and KPSeurologic function and KPS were assessed pre- and postoper-ely, before and after RT, and at each subsequent follow-up

it. Additionally, all surviving patients were telephoned andveyed with regard to their neurologic function and KPS usinginstitutional review boardapproved questionnaire. Neurologicction was assessed in accordance with the scale developed byCormick et al. (32). The performance status was assessed usingKarnofsky scale (33). No KPS values were recorded for oneiatric patient. Patients who had been employed before surgery

re also asked about their current work history.

thologic featuresll histologic sections available for evaluation were re-reviewed

a single neuropathologist (R.A.P.) at the Cleveland Clinic. Theors were graded according to the most recent World Health

ganization classification for astrocytomas (34). Only Grade I orade II tumors were studied.

rgeryll patients underwent decompressive laminectomy at the level

icated by previous imaging using a midline approach. Afterning the dura, a midline myelotomy was made, and the remain-of the surgery was performed with the assistance of an oper-g microscope in all but one case. In 13 cases, a biopsy was

en and sent for frozen section analysis, with one sent for

manent examination only. The myelotomy was then extended sorthe superior and inferior poles of the tumor, and the cord waspected for the presence of discrete surgical planes. In mostes, no such plane was encountered, and a decision was thende to either attempt to resect the tumor or terminate the proce-e. Subtotal resection (STR) and GTR were performed entirelyh standard microsurgical techniques in most patients (see TableAfter biopsy or attempted radical resection, watertight closure

the dura was obtained, and the fascia, subcutaneous tissue, andn were closed in standard fashion.

ross total resection was defined as complete removal of theor without any evidence of residual disease according to therative notes and any available postoperative imaging. Anything

s than a GTR was considered STR. All STRs performed in thislysis resulted in 75% removal, with the exception of oneection that resulted in only 25% removal.

diotherapyadiotherapy was delivered to the tumor and margin based onimaging results and intraoperative findings. The field length

ically encompassed the tumor and 35 cm above and below theor. The width was typically taken to be 2 cm on either side ofmost lateral aspect of the vertebral bodies. In 3 cases, a

e-down field was used for the last 3.6, 6, and 14.4 Gy. Theiation dose was delivered via PA fields for thoracic lesions,scribed to the spinal cord depth, and lateral fields for cervicalions, prescribed relative to the midline. In two cases (bothracic lesions), a three-field technique was used.

emotherapyo patient in this study received chemotherapy.

tistical analysisverall survival (OS) was measured from the date of surgery

il death or, for living patients, the last telephone interview,ical examination, or imaging study. Likewise, progression-free

vival (PFS) was measured from the date of surgery until tumorgression; patients without progression were censored on thee of their last clinical examination or imaging study. Theplan-Meier method was used to summarize the 5-, 10-, andyear OS and PFS (35). The logrank test was used to determineether a statistically significant difference existed between gen-, tumor extent, presence of syrinx, resection extent, symptomation, and the use of RT on OS and PFS. The correlationween age and pre- and postoperative neurologic function andS and survival was estimated using the Cox proportional hazarddel. The chi-square test was used to test for statistical signifi-ce; 95% confidence intervals (CIs) were also added to thevival rate and hazard ratio to address the variance of ourimation because of the small sample size. All tests were twoed, and p 0.05 was considered statistically significant. Sta-ical analyses were performed using the StatView softwarekage, version 5.0 (SAS Institute, Cary, NC).

RESULTS

inical findings on presentationOf the 14 patients, 7 were males. The median age atgnosis was 40.5 years (range, 5.277.2 years). The most

mmon presenting symptoms were weakness (71%), sen-

y disturbances (43%), pain (43%), and autonomic dys-

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93Low-grade spinal cord astrocytoma C. G. ROBINSON et al.ction (36%). The median duration of symptoms beforegnosis was 8 months (range, 0.1120 months). The initialaging diagnosis was made with myelography (3 patients,%), CT (1 patient, 7%), and MRI (10 patients, 71%).The most common tumor location was thoracic (11 pa-nts, 79%) followed by cervical (2 patients, 14%) andvicomedullary (1 patient, 7%). The extent of the spinal

rd tumor was measured as a function of the number ofrtebral bodies it spanned. The median tumor extent waso vertebral bodies (range one to six). No holocord

ors were present in this series. Six patients (43%) had aor-associated syrinx. A summary of patient characteris-

s is presented in Table 1.

rgical resultsAll 14 patients in this series underwent surgery for their

or. The median time to surgery from the date of theaging diagnosis was 38.5 days (range, 0595 days). Sur-ry was performed as previously described; 7 patients%) underwent biopsy, 6 (43%) underwent STR, and 1

tient (7%) underwent GTR. In all 6 patients with a tumor-ociated syrinx, the fluid was drained during surgical

ploration.Pathologic analysis revealed all 14 tumor specimens to be-grade astrocytoma, with 11 clearly Grade II and 3

ssified as low-grade astrocytoma, not otherwise specifieding to limited tissue sampling. None of the tumors dem-strated identifiable mitotic activity, vascular proliferationanges, or necrosis.Two patients (Patients 2 and 4) required repeat surgery.Patient 2, neurologic function began to worsen 11 years

Table 1. Patien

No. Age (y) Gender YearImagingmodality Sym

1 32 F 1980 Myelography Weak LLE2 38 M 1982 Myelography Weak BLE3 34 F 1983 Myelography Weak BLE

retention4 47 M 1984 CT Weak BLE5 57 F 1987 MRI Weak BLE

LLE, bo6 50 M 1988 MRI Numb RL7 41 F 1993 MRI Pain in ne8 33 F 1994 MRI Paralysis B9 40 M 1998 MRI Dysesthesi0 48 F 1999 MRI Weak LLE

parestheincontin

1 5 F 1999 MRI Weak BLE2 43 M 2000 MRI Weak RLE

erectile3 77 M 2001 MRI Weak BUE

frequenc4 24 M 2002 MRI Pain in ba

bbreviations: Pt. No. patient number; B bilateral; L lef

vicomedullary.er biopsy and RT, and repeat MRI suggested tumorgression. GTR, however, demonstrated an old hematoma

d necrosis. In Patient 4, neurologic function began torsen 15 years after STR and postoperative RT, and repeatI suggested tumor progression. Biopsy demonstrated

od clot and fibrous tissue.

resultsTen patients received postoperative RT as a part of theirtial therapy for the tumor. No patients received anyditional RT in their lifetime. RT was delivered as previ-sly described. The median time to the start of RT from thete of surgery was 32 days (range, 1287 days). Thedian dose delivered was 5020 cGy (range, 45005400y) in 28 fractions (range, 2530), with a median dose perction of 180 cGy (range, 170200 cGy). Of the 10tients who received postoperative RT, 3 (30%) wereated with 60Co, 1 (10%) with 4-MV photons, 5 (50%)th 6-MV photons, and 1 (10%) with 10-MV photons.Four patients did not receive postoperative RT. Of thesetients, 2 underwent biopsy, 1 underwent STR, and 1derwent GTR.

mplicationsSurgery. In 8 (57%) of the 14 patients, previous neuro-ic deficits immediately worsened or new deficits devel-

ed postoperatively. The most common complaint wasrsening of lower extremity weakness (4 patients, 29%).e symptoms were temporary in 5 (62.5%) of the 8 pa-nts but became permanent in the remaining 3 (37.5%).Neurologic function worsened immediately after the sec-

cteristics

at diagnosis

Symptomduration

(mo) Location Extent Syrinxb RLE, back pain 13 T9T10 2 Notic LLE 0.1 T5T9 5 Yesb LLE, urinary 24 T9T11 3 No

pain 1 T10T12 3 Nob R foot, paingency

36 T11 1 Yes

18 T6T7 2 Yeshoulder, vertigo 7 CM 1 Noumb T10 level 1 T8T11 4 No/LE shoulders 3 C3C4 2 No

b LLE,E, urinary

120 T12L1 2 Yes

collis 6 T1T6 6 Yesin thorax at T4,

tion48 T5T7 3 Yes

difficulty, urinaryncy

6 C4C5 2 No

LE 9 T10 1 No

right; UE upper extremity; LE lower extremity; CM aftproan

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94Table 2. Treatment and complications summaryt.o.

Time tosurgery (d) Extent Surgical technique

Secondsurgery Complications

Time toRT (d) Field

Dose (cGy), fraction,dose/Fx (cGy) Energy Complications

1 2 STR Microscope New dysesthesia BLE, lossof proprioception LLE

34 PA 5000, 25, 200 60Co Multiple rib fractures

2 0 Bx Frozen GTR at 11 y 1st surgery: Worseningweakness BLE; 2ndsurgery: E. colibacteremia

24 PA 5040, 28, 180 4 MV Worsening weaknessBLE

3 4 STR Microscope, frozen Worsening weakness BLE 29 PA 4930, 29, 170 60Co Multiple vertebralbody collapse insurgical/radiationsite

4 71 Bx Microscope, frozen Bx at 15 y 1st surgery: Worseningweakness BLE; 2ndsurgery: Permanentworsening of motorfunction

30 ND 4915, 26, 189 60Co

5 6 STR (25%) Microscope, frozen,laser.

53 PA 4500, 25, 180 10 MV

6 57 Bx Microscope, frozen,SEP

13 PA 5400, 30, 180 6 MV

7 595 Bx Microscope, frozen,SEP

New weakness BUE No RT

8 40 Bx Microscope, frozen 12 PA 5400, 30, 180 6 MV9 44 Bx Microscope, frozen Wound dehiscence, CSF

leakNo RT

0 23 STR Microscope, frozen,US

Worsening numbness BLEand paresthesias BLE

87 RPO/LPO/PA 4500, 25, 180 6 MV

1 6 GTR Microscope, frozen,SEP, CUSA, US

No RT

2 37 STR Microscope, frozen,SEP/MEP

New neurogenic bladder,neurogenic bowel, andLE DVT

No RT

3 112 STR Microscope, frozen Worsening weakness BLE 63 Lateral 5400, 27, 200 6 MV4 155 Bx Microscope, frozen 53 LPO/RPO/AP 5400, 30, 180 6 MV Decadron induced

AVN of both hipsand both ankles

Abbreviations: Bx biopsy; STR subtotal resection; GTR gross total resection; frozen frozen section analysis at surgery; SEP sensory evoked potential monitoring; MEP otor evoked potential monitoring; CUSA Cavitron ultrasound aspirator; US intraoperative ultrasound guidance; ND not determined; RPO right posterior oblique; LPO leftsterior oblique; DVT deep venous thrombosis; other abbreviations as in Table 1.

I.J.Radiation

Oncology

Biology

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95Low-grade spinal cord astrocytoma C. G. ROBINSON et al.d surgery in both patients who required repeat surgery fortative tumor recurrence; in both cases, symptoms weresented on last follow-up. Additional postoperative com-cations developed in 2 (14%) of the 14 patients that wererelated to their neurologic status and included woundhiscence, cerebrospinal fluid leak, lower extremity deepnous thrombosis, and gram-negative sepsis.Radiotherapy. All patients experienced some degree ofn discoloration in the radiation field, although none ex-rienced skin breakdown. In most patients, neurologicction improved or stabilized shortly after the adminis-

tion of RT. However, 1 patient developed complicationsring RT, and 2 patients developed complications moren one decade later. Patient 2 reported worsening bilateraler extremity weakness shortly after RT was initiated,

ich gradually improved in the months after treatment.e same patient later underwent GTR for worsening neu-ogic function and putative tumor progression on MRI, asscribed previously. He had originally received 5040 cGy28 fractions via a single PA field using 4-MV photons.ter the second surgery, his neurologic symptoms progres-ely worsened, and he died 5 years later of complicationsated to paralysis. Patient 4 also underwent a secondgery as a result of a similar presentation. However, hes still alive 4 years later. He had originally received 4915y in 26 fractions via an unknown field using 60Co.

herSome complications were not obviously attributable toher surgery or RT, but were likely exacerbated by both. Intient 3, multiple vertebral bodies within the operated andiated field started to collapse 18 years after treatment.ewise, not all complications came as a direct result ofgery or RT. Patient 14 underwent biopsy and postoper-ve RT for a T10 tumor. His neurologic status remainedble on steroids. However, several attempts to wean himm the steroids resulted in worsening pain. Although hes eventually tapered off the steroids, his hip and thenkle pain worsened. He was later diagnosed with avascularcrosis of both hips and ankles. Although at last follow-up,showed no signs of residual neurologic deficit, he had

ronic hip and ankle pain that had only recently comeder control with the use of multiple narcotics. Anothertient (Patient 1) recently began to have recurrent ribctures 23 years after receiving 5000 cGy in 25 fractions

a single PA field using 60Co energy. A review of theginal port films indicated the affected ribs were notectly in, or adjacent to, the radiation field.A summary of the treatment and resulting complicationsgiven in Table 2.

rvival analysisThree patients died during the period of analysis, with adian time to death of 9.1 years (range, 6.116.0 years).e cause of death was attributable to tumor progression intients 6 and 8 and radiation necrosis in Patient 2. Theaining 11 patients were alive at analysis, and all were denailable for follow-up at a mean of 10.2 years (range,23.4 years) after surgery.The OS rate at 5, 10, and 20 years was 100% (95% CI,0100%), 75% (95% CI, 45100%), and 60% (95% CI,96%), respectively. The PFS rate at 5, 10, and 20 yearss 93% (95% CI, 79100%), 80% (95% CI, 53100%),d 60% (95% CI, 2099%; Fig. 1a,b), respectively. Notistically significant correlation was found with OS orS for patient gender or age, presence of syrinx, tumortent, resection extent, symptom duration, RT use, or pre-postoperative KPS or neurologic function. However, fortients undergoing biopsy vs. more extensive resection, and toward significance at 10 years for both OS (60% vs.0%, p 0.0979) and PFS (60% vs. 100%, p 0.0746)s found.

ilure patternsFour patients developed MRI-diagnosed tumor progres-n at a median of 9.2 years (range, 0.915.7 years) aftergery. Two of the four underwent repeat surgery at 11 and.7 years after their initial surgery for imaging-diagnosed

. 1. Kaplan-Meier survival curves for (a) overall survival (OS)(b) progression-free survival (PFS) for all patients with low-

de astrocytoma of the spinal cord. Survival data for all patients,h 5-, 10-, and 20-year survival rates reported and 95% confi-

ce intervals in parentheses.

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96 I. J. Radiation Oncology Biology Physics Volume 63, Number 1, 2005urrence. Neither patient showed evidence of recurrentor in the second specimen. For the 2 remaining patients

o did not undergo pathologic confirmation of their pro-ssion, both died 1.7 and 5.2 years later of complicationsated to worsening neurologic function, and thus theyre considered true failures. Patient 6 developed recur-ce completely within the original tumor volume and

tient 8 did so both locally and three vertebral levels aboveoriginal site. Thus, the local control rate at 5 and 10

ars for our series was 89% and 71%, respectively. Amary of patient failure data is given in Table 3.

urologic function and performance status analysisOf the original 14 patients, 11 were alive at analysis, andwere interviewed; their neurologic function and KPS

re reviewed as described above. The median preoperativeurologic function was two (range, one to four), and thedian preoperative KPS was 80 (range, 6090). At fol--up, the median neurologic function was one (range, one

four), and the median KPS was 75 (range, 6090).During the immediate postoperative period, when all 14tients were alive, the neurologic function had worsened in57%) of 14 patients, and the KPS worsened in 9 (69%) ofpatients. The most common neurologic complaint wasrsening of sensory deficits, and the most common com-int overall was loss of ability to perform normal activitiesdaily living. In contrast, after RT, 10 (100%) of 10 and 9%) of 10 patients experienced stable or improved neu-ogic function and KPS, respectively. Compared with themediate postoperative period, at last follow-up, 11

Table 3. Summary of s

No.Survival

(y)Follow-up

(y)Cause of

deathTime to

failure (y)

Tifr

1 23.42 16.0 Necrosis

3 21.34 19.9

5 16.46 6.1 Tumor 0.9

7 9.58 9.1 Tumor 7.4

9 5.70 4.61 4.42 3.93 2.34 1.3bbreviations: GTR gross total resection; Bx biopsy.0%) of 11 and 8 (80%) of 10 patients experienced stableimproved neurologic function and KPS, respectively.ese numbers are somewhat misleading, however, becausepreoperative neurologic function had stabilized or im-

ved in 8 (67%) of 11 patients and KPS had worsened in50%) of 10 patients. This discrepancy resulted becauseeral patients developed significant worsening of neuro-ic function after surgery and never improved. For thoseatients with persistent worsening of neurologic function,ltimately worsened by 1 point on the McCormick scale,

d 1 by 3 points. Likewise, for the 5 patients with wors-ing KPS, the median change was 20 points, with only 1tient worsening by 30 points. The most common reason

worsening KPS was a declining ability to perform nor-l activities secondary to pain. In most cases, this pain wasilar in character to their presenting pain, but increased in

ensity and/or distribution. In a notable exception, the 1tient who developed steroid-induced avascular necrosis of

hips and ankles experienced a 30-point decline in KPSthe face of stable neurologic function.Of the 8 patients whom we queried about work history, 6ntinued to work a median of 5 years (range, 116 years)er treatment. Of the remaining 2 patients, 1 worked for 17ars before stopping secondary to worsening pain. Only 1tient unable to work immediately after treatment second-

to pain and weakness. Of the 11 patients who were aliveanalysis, 7 were ambulating without assistance, 3 re-ired a cane or walker, and 1 required a wheelchair. A

mary of the neurologic function and KPS measures issented in Table 4.

l and failure data

deathilure

Failure location Comments

Progression by imaging at11 y; GTR findings ofnecrosis and oldhematoma

Progression by imaging at15 y; Bx findings ofblood clot and fibroustissue

Local Progression by imagingno biopsy

Local plus 3 levelsabove original level

Progression by imagingno biopsy(10or

Ththepro5 (sev

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en

paforma

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Pt.No. Preoperative Postoperativ

1 80 502 80 503 80 604 90 70

5 80 80

6 80 707 90 808 60 409 70 70

10 70 7011 NA NA12 80 7013 80 5014 90 90

Abbreviations: KPS Karnofsk* McCormick scale.Table 4. Summary of neurologic function and performance status

KPS Neurologic function*Working now? How

many years aftersurgery? Reason

stopped?eBefore

RTAfterRT

Follow-up(mo)

Change(Preoperativeto follow-up) Preoperative Postoperative

BeforeRT

AfterRT

Follow-up(mo)

Change(preoperativeto follow-up)

60 70 80 0 2 4 3 3 2 0 NA (homemaker)70 80 Dead Dead 3 4 3 3 Dead Dead NA (dead)70 70 60 20 3 4 3 3 3 0 No, 17 y, pain80 80 70 20 1 4 3 2 4 3 No, 0 y, pain

weakness90 90 90 10 4 2 2 1 1 3 Yes, 16 years to

date70 70 Dead Dead 2 2 2 2 Dead Dead NA (dead)

None None 90 0 1 2 None None 1 0 Yes, 10 y to date50 50 Dead Dead 4 4 4 4 Dead Dead NA (dead)

None None 90 20 2 2 None None 1 1 Yes, 6 y to date70 70 90 20 1 2 2 1 1 0 Yes, 4 y to date

None None NA NA 4 3 None None 1 3 NA (child)None None 60 20 2 3 None None 3 1 Yes, 4 y to date

50 80 70 10 2 3 4 3 3 1 NA (retired)90 70 60 30 1 1 1 1 1 0 Yes, 1 y to date

y performance status; RT radiotherapy.

97Low

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98 I. J. Radiation Oncology Biology Physics Volume 63, Number 1, 2005DISCUSSION

We have reported on the survival and changes in func-nal status of patients with pathologically confirmedASC who were treated predominantly with limited re-tion and postoperative RT. This series differs from mostthat we included only those patients with pathologicallynfirmed low-grade astrocytomas. Our patient populations otherwise similar to the others described in the litera-e with regard to patient, tumor, and treatment factors.The use of adjuvant RT for spinal cord astrocytomas istified primarily because local recurrence remains themary pattern of treatment failure. Furthermore, consid-ble evidence has shown that patients undergoing STR forracranial astrocytoma benefit from adjuvant RT, thusplying a certain radioresponsiveness for this tumor. Thisplication has been further bolstered by evidence of aseresponse relationship; radiation doses 40 Gy haveen associated with improved local control (36). However,evidence has suggested additional local control or sur-al benefit with doses 50.4 Gy (15, 37). Thus, theical radiation doses given for spinal cord astrocytomas4550.4 Gy in 1.8-Gy fractions.

In our study, the 5- and 10-year OS rate was 100% and 75%5- and 10-year PFS rate was 93% and 80%, respectively,patients with LGASC. These results compare favorably

th other reported survival rates for patients undergoing lim-d resection and RT. When that body of the literature wasiewed carefully, and the data relating only to LGASC wereracted, we found OS rates of 6191% and 4391% at 5 andyears, respectively (613, 15, 16, 37). Thus, our resultsfirm that for patients with low-grade astrocytoma, biopsy or

R followed by RT can produce long-term OS and PFS.Our OS and PFS rates were also equivalent to thoseorted in a number of recent surgical series dealing withASC. Because of the advances in technology that have

curred during the past two decades within the neurosur-al field, surgeons can now perform more extensive spinalor resections without the high morbidity previously

ociated with such procedures. Several authors have re-tly reported 5-year OS rates of 7289% in adults and

100% in children who underwent extensive resectionthout adjuvant RT. These data are, overall, less maturen those reported for limited resection and postoperative, although the results are promising. Thus, many authors

w recommend that whenever possible, patients undergoical resection for LGASC without postoperative RT (10,

19, 21, 22, 24, 25, 28, 29, 31, 38). These data must beerpreted carefully, however, because anywhere from 4%53% of patientseven those in these surgical seriesnerally receive RT at some point in their treatment (17, 2830, 39). In those patients who might safely undergomplete tumor resection, a watchful waiting strategy may,fact, be appropriate.Although both surgery and RT have recognized short-d long-term risks associated with their use, the reporting

complication rates for LGASC has been inconsistent. Inr series, 57% of the patients reported that their neurologicction had worsened after surgery and 14% developeder surgical complications. Of these patients, 38% had

rsistent worsening of neurologic function at last follow-. Our reported surgical complication rate was greater than

range of 513% reported elsewhere in the literature.wever, many studies did not document worsening neu-ogic function as a complication (17, 19, 2325, 27, 28,, 31, 39).In those patients who received postoperative RT in ouries, 2 patients underwent repeated surgery for suspectedor recurrence after prior surgery and postoperative RT.

th had progressive decline in neurologic function andaging evidence of tumor progression. Neither had evi-nce of recurrent tumor on repeat surgery, but were insteadnd to have clear evidence of necrosis in one and scarringthe other. Both patients had received typical radiationses and fractions of 50 Gy in 28 fractions and 49 Gy in 26ctions. The patient with necrosis on biopsy developedgressively worsening neurologic function and ultimatelyd of complications related to paralysis, and, thus, that

tients case was deemed true radiation myelopathy. Thetient with scarring on biopsy was alive at last follow-up,th poor lower extremity motor function that developedmediately after his second surgery, and has remainedble. Therefore, our rate of radiation myelopathy was 7%of 14). The incidence of myelopathy as reported else-ere is dose related, with rates reported using typicalctions from 0.2% to 0.5% after 50 Gy to 1% to 5% afterGy (24, 40, 41). Although the tolerance dose producing

of a specific radiotoxic effect within 5 years afteratment (TD 5/5) using conventional fractionation hasen traditionally reported as 4550 Gy (42, 43), reviews ofman data have suggested that doses of 45 Gy with con-ntional fractionation results in almost no myelopathy (44,). A better estimate for a TD 5/5 risk of myelopathy withnventional fractionation may be closer to 5761 Gy (44,), suggesting that the spinal cord may be irradiated safelythe accepted doses of radiation tolerance and even greater

to 55 Gy) without an increased complication risk (14,, 46). Although the general rule is that a dose reductionuld accompany increases in target volume, little clinical

ta have supported this for the spinal cord (47, 48). Noond malignant tumors were reported in our series. One

ssible method to reduce the complications due to RTuld be to implement more conformal techniques. Be-se astrocytomas, even low-grade varieties, are frequentlyltrative to some extent, the radiation field has been

ditionally set to encompass the gross tumor volume and argin that inevitably includes normal cord. Thus, eventh conformal techniques, the normal cord immediatelyrounding the tumor will not be spared. However, con-mal techniques will spare a larger proportion of otherrounding normal tissue, thereby reducing the rate oferall radiation toxicity to other systems such as the GIct, kidney, and soft tissue.

Most authors have reported at least some functional status

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livtheoverall worsening KPS, fully 75% of the patients continuedto work, with 1 patient working 17 years before finally

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umented LGASC, treated with modern neurosurgical andRT techniques, should be undertaken.

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99Low-grade spinal cord astrocytoma C. G. ROBINSON et al.REFER

American Cancer Society. Cancer facts and figures 2004.Atlanta: American Cancer Society; 2004.Winn HR, Youmans JR. Youmans neurological surgery. 5thed. Philadelphia: WB Saunders; 2004.Miller DC. Surgical pathology of intramedullary spinal cordneoplasms. J Neurooncol 2000;47:189194.Malis LI. Intramedullary spinal cord tumors. Clin Neurosurg1978;25:512539.Epstein FJ, Farmer JP. Pediatric spinal cord tumor surgery.Neurosurg Clin North Am 1990;1:569590.Minehan KJ, Shaw EG, Scheithauer BW, et al. Spinal cordastrocytoma: Pathological and treatment considerations. J Neu-rosurg 1995;83:590595.Lee HK, Chang EL, Fuller GN, et al. The prognostic value ofneurologic function in astrocytic spinal cord glioma. Neuroon-col 2003;5:208213.Rodrigues GB, Waldron JN, Wong CS, et al. A retrospectiveanalysis of 52 cases of spinal cord glioma managed withradiation therapy. Int J Radiat Oncol Biol Phys 2000;48:837842.McLaughlin MP, Buatti JM, Marcus RB Jr, et al. Outcomeafter radiotherapy of primary spinal cord glial tumors. RadiatOncol Invest 1998;6:276280.Nishio S, Morioka T, Fujii K, et al. Spinal cord gliomas:Management and outcome with reference to adjuvant therapy.J Clin Neurosci 2000;7:2023.Jyothirmayi R, Madhavan J, Nair MK, et al. Conservativesurgery and radiotherapy in the treatment of spinal cord as-trocytoma. J Neurooncol 1997;33:205211.

Shirato H, Kamada T, Hida K, et al. The role of radiotherapy 22.ES

in the management of spinal cord glioma. Int J Radiat OncolBiol Phys 1995;33:323328.Hulshof MC, Menten J, Dito JJ, et al. Treatment results inprimary intraspinal gliomas. Radiother Oncol 1993;29:294300.Kopelson G, Linggood RM. Intramedullary spinal cord astro-cytoma versus glioblastoma: The prognostic importance ofhistologic grade. Cancer 1982;50:732735.Linstadt DE, Wara WM, Leibel SA, et al. Postoperative ra-diotherapy of primary spinal cord tumors. Int J Radiat OncolBiol Phys 1989;16:13971403.Cooper PR. Outcome after operative treatment of intramedul-lary spinal cord tumors in adults: Intermediate and long-termresults in 51 patients. Neurosurgery 1989;25:855859.Jallo GI, Danish S, Velasquez L, et al. Intramedullary low-grade astrocytomas: Long-term outcome following radicalsurgery. J Neurooncol 2001;53:6166.Innocenzi G, Salvati M, Cervoni L, et al. Prognostic factors inintramedullary astrocytomas. Clin Neurol Neurosurg 1997;99:15.Epstein FJ, Farmer JP, Freed D. Adult intramedullary astro-cytomas of the spinal cord. J Neurosurg 1992;77:355359.Constantini S, Houten J, Miller DC, et al. Intramedullaryspinal cord tumors in children under the age of 3 years.J Neurosurg 1996;85:10361043.Constantini S, Miller DC, Allen JC, et al. Radical excision ofintramedullary spinal cord tumors: Surgical morbidity andlong-term follow-up evaluation in 164 children and youngadults. J Neurosurg 2000;93:183193.asure in their analysis. The most commonly reportedctional measures are neurologic function, typically mea-ed with the McCormick or Cooper and Epstein scales,

d performance status, using the Karnofsky scale (32, 33,). In a complete review of the RT and surgical literature

spinal cord astrocytoma, we found that the medianorted rate of stable or improved functional status at lastlow-up was 73% (range, 2791%), with no observableference between the different treatment modalities (7, 8,13, 17, 19, 21, 25, 2831, 37). We reported comparablees from our series, with stable or improved neurologicction in 73% and KPS in 50%. The reasons why a high

rcentage of our patients had worsened KPS at last fol--up are unclear. Compared with earlier series withater mortality rates, our patients may have lived long

ough to develop long-term consequences of extensivegery with RT, which can result in vertebral body col-se, spinal deformity, and so forth. The vast majority ofdies, our own included, have reported on patients treatedth older surgical and RT techniques. With the use ofdern neurosurgical and conformal RT methods, many ofse long-term side effects may be avoided.As an additional quality-of-life measure, we asked thoseing patients who were employed before surgery whethery were still able to work. Surprisingly, even in the face ofiring secondary to pain, and only 1 patient unable to workstoperatively. Even with such issues as pain, motor orsory disturbances, and other chronic problems related toir tumor or treatment, most patients in this series were

le to adapt and continue to function at a relatively highel. Thus, only with the routine application of multiplectional measurements can the effects of our treatmentsly be measured.

CONCLUSIONOn the basis of the most recent literature and our ownperience, we believe it is reasonable to watch closelytients with LGASC in whom GTR (confirmed with post-erative imaging) has been performed. In patients whove undergoing anything less than GTR, sufficient evi-nce has shown that long-term OS, PFS, neurologic func-n, and KPS can be improved with the addition of RT. Forse patients, adjuvant RT to 50 Gy in 1.8-Gy fractionsuld be delivered, preferably with conformal techniques

minimize the dose to the normal surrounding structures.nctional status measurements and complications shouldmeticulously recorded to elucidate further the relative

ks and benefits of the various treatment options. Totermine the optimal treatment of these rare tumors, alti-institutional analysis of only those patients with doc-Merchant TE, Kiehna EN, Thompson SJ, et al. Pediatric

low-grade and ependymal spinal cord tumors. PediatrNeurosurg 2000;32:3036.

23. Bouffet E, Pierre-Kahn A, Marchal JC, et al. Prognosticfactors in pediatric spinal cord astrocytoma. Cancer 1998;83:23912399.

24. OSullivan C, Jenkin RD, Doherty MA, et al. Spinal cordtumors in children: Long-term results of combined surgicaland radiation treatment. J Neurosurg 1994;81:507512.

25. Przybylski GJ, Albright AL, Martinez AJ. Spinal cord astro-cytomas: Long-term results comparing treatments in children.Childs Nerv Syst 1997;13:375382.

26. Reimer R, Onofrio BM. Astrocytomas of the spinal cord inchildren and adolescents. J Neurosurg 1985;63:669675.

27. Rossitch E Jr, Zeidman SM, Burger PC, et al. Clinical andpathological analysis of spinal cord astrocytomas in children.Neurosurgery 1990;27:193196.

28. Cristante L, Herrmann HD. Surgical management of intramed-ullary spinal cord tumors: Functional outcome and sources ofmorbidity. Neurosurgery 1994;35:6974.

29. Brotchi J, Dewitte O, Levivier M, et al. A survey of 65 tumorswithin the spinal cord: Surgical results and the importance ofpreoperative magnetic resonance imaging. Neurosurgery 1991;29:651657.

30. Guidetti B, Mercuri S, Vagnozzi R. Long-term results of thesurgical treatment of 129 intramedullary spinal gliomas.J Neurosurg 1981;54:323330.

31. Goh KY, Velasquez L, Epstein FJ. Pediatric intramedullaryspinal cord tumors: Is surgery alone enough? Pediatr Neuro-

32.

33.

34.

35.

36.

and postoperative irradiation. Int J Radiat Oncol Biol Phys1985;11:19331939.

37. Kopelson G, Linggood RM, Kleinman GM, et al. Manage-ment of intramedullary spinal cord tumors. Radiology 1980;135:473479.

38. Abdel-Wahab M, Corn B, Wolfson A, et al. Prognostic factorsand survival in patients with spinal cord gliomas after radia-tion therapy. Am J Clin Oncol 1999;22:344351.

39. Samii M, Klekamp J. Surgical results of 100 intramedullarytumors in relation to accompanying syringomyelia. Neurosur-gery 1994;35:865873.

40. Rampling R, Symonds P. Radiation myelopathy. Curr OpinNeurol 1998;11:627632.

41. Marcus RB Jr, Million RR. The incidence of myelitis afterirradiation of the cervical spinal cord. Int J Radiat Oncol BiolPhys 1990;19:38.

42. Phillips TL, Buschke F. Radiation tolerance of the thoracicspinal cord. Am J Roentgenol Radium Ther Nucl Med 1969;105:659664.

43. Wara WM, Phillips TL, Sheline GE, et al. Radiation toleranceof the spinal cord. Cancer 1975;35:15581562.

44. Schultheiss TE, Stephens LC. The pathogenesis of radiationmyelopathy: Widening the circle. Int J Radiat Oncol Biol Phys1992;23:10891093.

45. Schultheiss TE, Kun LE, Ang KK, et al. Radiation response ofthe central nervous system. Int J Radiat Oncol Biol Phys1995;31:10931112.

46. Chun HC, Schmidt-Ullrich RK, Wolfson A, et al. External

47.

48.

49.

100 I. J. Radiation Oncology Biology Physics Volume 63, Number 1, 2005surg 1997;27:3439.McCormick PC, Post KD, Stein BM. Intradural extramedul-lary tumors in adults. Neurosurg Clin N Am 1990;1:591608.Karnofsky D, Abelman W, Craver L, et al. The use of nitrogenmustards in the palliative treatment of carcinoma. Cancer1948;1:634656.Kleihues P, Cavenee WK, et al., for the International Agencyfor Research on Cancer. Pathology and genetics of tumours ofthe nervous system. Lyon: IARC Press; 2000.Kaplan E, Meier P. Nonparametric estimation from incom-plete observations. J Am Stat Assoc 1958;53:457448.Garcia DM. Primary spinal cord tumors treated with surgerybeam radiotherapy for primary spinal cord tumors. J Neuroon-col 1990;9:211217.Schultheiss TE, Stephens LC, Ang KK, et al. Volume effectsin rhesus monkey spinal cord. Int J Radiat Oncol Biol Phys1994;29:6772.van den Aardweg GJ, Hopewell JW, Whitehouse EM. Theradiation response of the cervical spinal cord of the pig:Effects of changing the irradiated volume. Int J Radiat OncolBiol Phys 1995;31:5155.Cooper PR, Epstein F. Radical resection of intramedullaryspinal cord tumors in adults: Recent experience in 29 patients.J Neurosurg 1985;63:492499.

LONG-TERM SURVIVAL AND FUNCTIONAL STATUS OF PATIENTS WITH LOW-GRADE ASTROCYTOMA OF SPINAL CORDINTRODUCTIONMETHODS AND MATERIALSPatient populationAssessment of neurologic function and KPSPathologic featuresSurgeryRadiotherapyChemotherapyStatistical analysis

RESULTSClinical findings on presentationSurgical resultsRT resultsComplicationsSurgeryRadiotherapy

OtherSurvival analysisFailure patternsNeurologic function and performance status analysis

DISCUSSIONCONCLUSIONREFERENCES