Radiation and ANs - Gareth ' research project

[Guest guest]

Hi all those who wanted more details:

This is the answer about the research project into radiation in Nf2 ANs.

Don't know yet how to get a copy of the British Journal of Cancer but will

try.

a

Dear a

Mike Baser is the first author on the paper. He used the 350 people

on our UK database + a German population + California, New York,

Denver and one or two other centres in the US. It is published in

British journal of Cancer 200: 82; 998.

Best wishes

Gareth

[Guest guest]

Thanks a. A medical library should have copies of the British Journal of

Cancer. I will try and get a copy of the article too.

----------

From: a Tweedy

Sent: Friday, May 05, 2000 6:09 PM

To: Nf2 Crew

Subject: Re: Radiation and ANs - Gareth ' research project

Hi all those who wanted more details:

This is the answer about the research project into radiation in Nf2 ANs.

Don't know yet how to get a copy of the British Journal of Cancer but will

try.

a

[Guest guest]

a and Crew,

I finally got hold of the article on RS and cancer in the British Journal of

Cancer. It was really a " Letter to the Editor " and the study seems more like a

survey. I'm not sure exactly where the numbers are coming from as there is some

" extrapolating " of data being done. I'll send a note to Lunsford for comment.

I scanned the letter and have shown it below. It did not come out perfect but I

hope it makes a little sense. The paper copy I has says you can get the article

from the web site http://www.idealibrary.com

Good luck!

--------------------------------------------------------

Letter to the Editor

Neurofibromatosis 2, radiosurgery and malignant nervous system tumours

Sir,

Neurofibromatosis 2 (NF2) is a rare (1:40 000) autosomal dominant disease that

is caused by mutations of the NF2 tumour suppressor gene. NF2 is characterized

by benign nervous system tumours such as vestibular schwannomas (VSs),

intracranial meningiomas and spinal tumours. Kondziolka et al (1998) reported

the outcomes of radiosurgery for unilateral sporadic VSs, but NF2 patients were

excluded and follow-up was limited. The consequences of radiosurgery for

histologically benign NF2 tumours merit study due to the mutagenic potential of

ionizing radiation. Somatic mutation could contribute to the transformation or

acceleration of existing tumours. and to the development of secondary tumours,

because NF2 patients have an inactivated germ-line NF2 allele. Ionizing

radiation is known to have such effects in hereditary retinoblastoma (Wong et

al, 1997). We conducted this study because the prevalence of, and risk factors

for, malignant nervous system tumours in NF2 are unknown.

We surveyed genetics. otolaryngology and neurology/neursurgery centres in North

America and Europe with a total of 1348 NF2 patients. There were nine malignant

nervous system tumours in the estimated 1242 NF2 patients who did not have

previous radiosurgery. This prevalencc of 725 per 10e5 (95% confidence interval

(CI) 253 - 1197 per 10e5) is significantly greater than the population

prevalence of 1.13 per l0e5 (95% CI 1.09 - 1.15 per 10e5) (SEER Program

Public-Use CD-ROM, 1998). There were five malignant peripheral nerve sheath

tumours (MPNSTS). two tnalig n ant men in emoinas. one ma lien ant ependymotna

and one atiaplastie astroeytonia (median age at tumour diagnosis. 14 years;

range 7-35 years). The population prevalences of these tumours are MPNST. 0.00

per 10e5; malignant meningioma, 0.42 per 10e5; malignant ependymoma, 0.05 per

10e5'; and anaplastic astrocytoma, 0.66 per 10e5 (SEER Program Public-Use

CD-ROM, 1998). Thus. NF2 patients have a significantly increased prevalence of

MPNST (402 per 10e5; 95% Cl 50 - 754 per 10e5).

After radiosurgery for benign tumours. five NF2 patients developed malignant

tumours in high-dose areas (three MPNSTs. one malignant mentngioma and one

malignant ependymoma; median age at tumour diagnosis, 32 years). In three large

NF2 patient series that were included in this study. 47 of 599 patients (7.8%)

received radiosurgery (DGR et al, unpublished data). By extrapolation,

about 106 of the 1348 patients in this study would have received radiosurgery,

suggesting that malignant transformation in five of 106 patients was

radiation-associated (4717 per 10e5; 95% CI 681 - 8753 per 10e5).

Radiosurgery is typically used for NF2 patients with aggressive tumours, or who

refuse surgery, or who are poor surgical risks or elderly. The results of this

study should not be used to interdict radiosurgery for these patients; in

addition, the results of this study reflect past exposures and lower doses of

ionizing radiation are used in current radiosurgery protocols. However,

observation without surgery, decompression without tumour removal, and surgical

excision are the preferred therapies for other NF2 patients, particularly those

who are young.

ACKNOWLEDGEMENTS

We thank the NF2 patients for their participation and Dr JM Friedman for many

helpful comments.

ME Baser', DGR 2, RK .Jacklerr, E Sujansk~'4 and

A Rttl,e,t.steinr

'Los Angeles. USA, 2Departtnent of Medical Ge,teric.s, St Mars ~s

Hospital. Mautclte.ste; UK, 'Departmeutt.s of Otolarv,tt~olot,'v nun

Neurological St,r~,,'erv, Unit'er.sitv of Calif~.'rutia at San Franusco,

Sa,t Francisco, CA, USA, 4Division of Geutetic Services, Univer.siry

(If Colorado Health Sciences Center/Children s Hospital. Den vcr. CO. USA,

'Departnte~tt '?f Neumlogv, Mt Sinai School t~f Medicine, New York, NY, USA

REFERENCES

Kottdeiolka B. Lunsford LB. McLaughlin MR and Flickingcr IC) 1998) Long-Lerm

outcomes alter radiosurecry ('or acoustic ncuroma. N Euc,~1 J Mcd 339:

14261433

Surveillance. Epidemiology and End Results (SEER) Progratll Public-Use CD-ROM

((9731995). National Cancer Institute. DCPC. Survci I lance Progrant. Cancer

Statistics Branch. released April 1998. based on the August 1997 submission.

Rates are for 1986-1995 data age-adjusted to the (98(1 US standard Wong FL.

Boice ID Jr. Ahrarnson DH en al ((997) Cancer incidence after

reti nohlastorna: radiation dose and sarcoma risk. iA/VIA 278: (2621267

998