Volume 7, Number 2ISSN 1086-427X

IMRT..............................................1Fast Facts .......................................3

Radioablation...................................6Radiation Injury...........................12Patient Stories .............................2,5

IRSATM

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brain

talk

brain

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InternationalRadiosurgery

SupportAssociation

Intensity modulated radiation therapy (IMRT) is abrand-new method of administering external beam radi-ation therapy to treat tumors. It represents a significantadvance in radiation therapy. IMRT’s earliest use totreat a mere handful of patients was less than ten yearsago. Only in the past year or two has it become avail-able at more than a few specialized centers. Its in-creasing use at an ever-expanding number ofcenters has been regarded with trepidation bysome, for there are significant differences betweenthis form of treatment and previous forms of radi-ation therapy.

These concerns arise from several relevantfacts. IMRT requires a great deal of specializedand expensive equipment and computer soft-ware, and currently is relatively inefficient todeliver, compared with other forms of externalbeam radiation therapy. More computer time and personneltime is required to plan a treatment and perform quality assurance forIMRT than for a treatment with 3D conformal radiation therapy (3D CRT). Thisincreases the costs of offering this sophisticated treatment.

To administer high quality IMRT, no component of quality assurance can be neglected.Quality assurance concerns exist because the specialized equipment that is needed for IMRTmust perform flawlessly to deliver the treatment as prescribed. The promise of IMRT isgreat, but until greater experience and familiarity is gained with this technique, physicians,physicists, and patients would do well to proceed with caution.

RadiotherapyFor decades, radiotherapy was given with simple beam arrangements that minimized the

chance of the X-ray beam missing the tumor. Typically, the process started with a physiciandrawing radiation therapy portals on X-ray films of the patient. This indicated where thebeams were to be directed. All relevant calculations were performed by hand, and the radia-tion dose was usually only calculated at one or several points of interest.

It was exceptional to treat a patient with beams that were not all oriented in the sameplane. Radiation therapy treatments were given with the expectation that the position of thetumor in the patient and the position of the patient on the treatment table would not be pre-cisely the same every day.

At this time, a hallmark of sophisticated treatments included the use of lead blocks to pre-vent uninvolved tissues from receiving harmful irradiation, and when appropriate, devicescalled wedges would be used to increase the uniformity of the radiation dose in the volumeof concern by differentially attenuating the radiation beam intensity in one direction. Athird type of device called a compensator could be painstakingly fabricated.

A compensator is a device that attenuates the intensity of the beam in areas where thebeam must traverse less tissue to reach the target. These devices were helpful in assuring auniform dose of radiation was delivered when treating anatomic regions where the externaltissue contours changed sharply, but the intensive labor required to make them precludedtheir common use.

Compensators, lead blocks, and wedges were regarded as improvements, but they led tomany patients inadvertently being mistreated through a lack of appreciation of the new po-tential for error these devices introduced. Errors could occur by putting in the wedge side-ways or backwards, or by using the wrong wedge, leading to inappropriate and possiblyharmful changes in the radiation dose distribution. It was also possible to use the wrong setof lead blocks, which could result in the tumor being shielded from radiation or in normaltissues getting radiation by mistake.

Dr. Jonathan Knisely

Continued on page 3

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IMRT and RADIOABLATION

IMRT - Intensity Modulated Radiation Therapy

2 Brain Talk, Volume 7, Number 2

StereotacticRadiosurgery

Stereotactic radiosurgery is not surgery.The skull is never opened. Radiosurgeryinvolves the use of precisely directed sin-gle fractions of radiation to create lesionswithin the brain or to treat tumors or vas-cular malformations with minimal dam-age to surrounding structures or tissues.

This works by delivering a relativelyhigh dose of radiation in one session tothe target with scalpel-like precision. Thedose is designed to injure or kill the cellsor their supporting blood vessels, whileminimizing its effect on surroundinghealthy tissue. The radiation distorts thecells’ DNA, causing them to lose the abil-ity to replicate themselves. The safety andclinical effectiveness of this techniquehas been established since 1968 in over200,000 treated individuals.

The benefits include: No risks of infec-tion or anesthesia reactions; virtually nopain; reduced costs; and an immediate re-turn to normal activities.

Radiosurgery may or may not be ap-propriate for your condition. It may beused as the primary treatment or recom-mended in addition to other treatmentsyou may need. Only a treating neurosur-geon can make the evaluation as towhether you can be treated. Some of themost common indications for treatmenttoday are:

• Arteriovenous/vascular malformations• Meningiomas• Acoustic neuromas• Pituitary and pineal tumors• Metastatic tumors• Glial and astrocytoma tumors• All other malignant & benign tumors• Trigeminal neuralgia• Parkinson’s tremors/rigidity• Functional disorders

DisclaimerAll technical information regarding any

technology published by IRSA, in thispublication or elsewhere, has been pro-vided by the manufacturer of the equip-ment. The publisher does not warrant anyinstrument or equipment nor make anyrepresentations concerning its fitness foruse in any particular instance nor anyother warranties whatsoever.

22-Year Survivor of Esthesioneuroblastoma Is an Active Mother

Editor ’s note: thisstory was kindly con-tributed by Linda. Weare pleased to updateher story for those ofyou who have re -peated ly asked howshe is doing. S incewe first brought herstory to you in 1998,

cancer ce l l s have me ta s ta s i z ed t oLinda’s spinal cord. She is current lylooking for fu ture noninvas ive t reat -ments.

Twenty-two years ago, at age 26,I was d iagnosed wi th a ra re headand neck cancer called esthesioneu-roblastoma. I had a craniofacial re-section and thought it was gone. Itcame back ten years later and I hadanother craniofacial resection, andth i s t ime my r i gh t eye was r e -moved. I thought I was cured, asmy doctor told me this was the mostlikely scenario. Well, this rarest ofa l l head and neck cance r s i s no tcurable, and has a high return rate.I t i s so r a r e t ha t on ly abou t 200people in the entire country have it.I have the dubious d i s t inc t ion ofbe ing the longes t l i v ing pa t i en t !Tha t sounds n ice , bu t i t i s rea l lyve ry s ca ry, wonde r ing when myluck will run out.

Well, it appeared to almost haverun out in June of 1997. A tumorad j acen t t o my op t i c ne rve hadbegun growing. I had surgery on itbut they could not remove the en-t i re tumor wi thout caus ing me tolose the structure that held my eyeintact. So, after the surgery it wasrecommended tha t I have GammaKnife surgery to reduce the rest ofthe t umor. I had the su rge ry s ixmonths later, and i t was a breeze.The tumor shrank away and my ra-d i a t i on onco log i s t t o ld me t het rea tment was to ta l ly success fu l .Bu t t h i s was wrong , a s I wou ldlearn four years later!

In December of 2000, dur ing arou t i ne MRI , I l e a rned t ha t t hetumor was again growing! I askedmy phys i c i an how cou ld t h i s be ,and he expla ined tha t the marg inthat was adhered to in targeting myop t i c ne rve a l l owed fo r my eye -sight to be preserved but may have

allowed a very small amount of thetumor t o ex i s t t ha t cou ld no t beseen with a scan. The tumor is notinvading the nerve yet, but it is justa matter of time. So, we are closelyfo l lowing i t w i th MRIs and I ampaying careful at tention to my vi-sion, which is still fine. My tumorst end t o g row toward t he pa th o fleas t res is tance, so maybe my vi-sion will remain intact for a longertime than anticipated. I am prayingfor that.

Meanwh i l e , i n May o f 2001 Ilearned that I have 32 tumors on mysp ina l co rd , me ta s t a se s f rom mybrain! No other patient with esthe-s ioneurob las toma has eve r had asp ina l me t a s t a s i s because t heydon ’ t l i ve t ha t l ong , I am to ld .After months of research and con-sul ta t ions wi th doctors a l l acrossthe country, I opted for full spinalradiat ion, at a dose that would besa fe fo r my sp ina l co rd , bu t t ha twou ld hope fu l l y do t he t r i ck o fshr ink ing the tumors . Two la rgeones were severely compressing myspinal cord. After seven weeks oftreatments, and an unexpected two-week in-hospital stay, I learned inJanuary that the treatments weren’tworking! Now, the two larger tu-mor s a r e compre s s ing my sp ina l

Linda

Continued on page 9

3Brain Talk, Volume 7, Number 2

IMRTContinued from page 1

With the advent of cross-sectionalimaging (CT and MR scans), and theintegration of high speed computersinto radiotherapy departments, it be-came possible to conceive and evalu-ate on a computer screen increasinglycomplex treatments that included leadblocks, wedges, and coplanar (2.5Dplans) or noncoplanar (3D plans)beams.

At this time, the process for plan-ning radiation shifted from a physi-cian drawing on a piece of X-ray filmto a physician using a mouse on acomputer screen display of a CT scanto indicate where the tumor was locat-ed.

Computer-generated plans weredeveloped with the assumption thatthe anatomy shown on the imagingstudy used to plan the treatment didnot change over the weeks to monthsthat therapy took to deliver. The abil-ity to deliver the more complex treat-ments that could be displayed on acomputer screen in dazzling color wasfacilitated by improvements in com-puter-controlled radiation treatmentdelivery.

Computers could keep a treatmentfrom proceeding if human error hadled to a wedge being positioned incor-rectly or if the wrong tray of blockswas inserted by mistake, or if any oneof a number of other potential errorshad occurred in positioning the ma-chine and the patient for treatment.

The desire grew among radiationoncology physicians to decrease nor-mal t issue irradiat ion. The tumorcould be seen much more clearly onCT scans than on plain X-rays, andthere was no longer a need to treat asmuch normal tissue to make sure thatthe tumor was not missed. However,by evaluating sequential imagingstudies on their pat ients , doctorsagain became aware of the fact thatthere is organ movement within a pa-tient’s body during radiation treat-ment. This movement not only occurson an ongoing basis due to breathing,but also occurs from other voluntaryand involuntary muscle action.

This movement of the tumor and ofnormal t issues, together with theaforementioned minor inconsisten-cies in daily patient positioning caneasily lead to inaccurate block designthat will actually protect the tumor

from radiation or allow overtreatmentof normal tissues.

In many situations, the dose of ra-diation therapy that can be safely de-livered to a tumor is restricted by thedose that the normal tissues will re-ceive. It is axiomatic that if a largevolume of normal tissues receives ahigh dose of irradiation, the treatmentwill be less well tolerated than if asmaller volume of normal tissues re-ceives a low dose of irradiation.

The dose of radiation that normaltissues can tolerate is frequently thelimiting factor in how much radiationtherapy can be given to the tumor.This is important, because a curativetreatment may require that very highdoses be given to the tumor.

The recognition of the need to tryto design blocks that maximally pro-

tect normal tissues while not protect-ing the tumor (even with uncertaintyabout day-to-day posi t ioning andorgan movement) led to the develop-ment of what is now relatively com-monly used for many tumors, 3Dconformal radiat ion therapy (3DCRT). The potential benefits of thisform of sophisticated treatment in-clude protection of normal tissues inthe vicinity of the tumor while notprotecting the tumor.

Beams can be directed at the tumorfrom a number of different directionsto avoid giving excessive radiationdoses to certain normal tissue struc-tures that may be close to the tumor.Devices are commonly used to helpimmobilize and position the patientfor treatment. Blocks and wedges areused together in nearly al l beamsused.

All the treatment techniques thathave been described above involvethe use of sophisticated computerizedimaging and computerized planning,but the planning is carried out by awell-trained individual (a physicist,physician, or most commonly, a med-ical dosimetrist) who will, through aprocess of trial and error, select theangles from which the X-ray beamswill be delivered, design blocking,and adjust the relative time that eachbeam will be used to treat the tumor toachieve the physician’s goal.

The radiation oncologist will re-view and direct modifications beforefinally approving the plan which willbe used to deliver the prescribed radi-ation. This form of planning is com-monly called “forward planning,” andit is very different from the planningwhich is used for IMRT.

IMRTIMRT is a form of 3D CRT that also

uses sophist icated computerizedimaging and high-speed computers.There are several very important dif-ferences, however, and one is that theprocess of planning occurs in a differ-ent sequence, and has been termed“inverse planning” or “optimizedplanning.” The prescription is givento the computer before the plan isgenerated. The physician must con-tour the target and all normal tissueson a number of CT slices. Only by de-termining in 3D where all the normaltissues are and where the tumor tissueis, will the software be able to devel-op a plan that will meet the clinician’sgoals.

Clear and definite goals and para-meters must be given to the treatmentplanning computer before it plans thetreatment, including the desired doseto the tumor, whether or not a nonuni-form dose within the tumor is accept-able (i.e., “cold spots” or “hot spots”)and the dose ranges that are accept-able for normal tissues. A plan is thengenerated that will attempt to fulfillthe physician’s goals. When the planis reviewed by the physician, theremay be a clear need for modificationof the directives given to the comput-er, as the computer may have devel-oped an (unacceptable) solution thatwould never have even been initiatedby a skilled user.

A very significant difference be-tween IMRT and other forms of 3DCRT is contained in the f irs t two

Continued on page 4

◆ The goal of radiation is to improve local tumor control.

◆ Radiation disrupts the genetic material that cells need to divide and grow.

◆ Radiation kills over time, as the cells try to divide.

◆ A faster growing cell (higher grade tumor) will show earlier cell death after radiation than a slow growing tumor.

◆ Radiation disrupts the genetic material within cells that regulates fluids.

◆ Swelling or edema can occur as the damaged cells are unable to regulate fluids.

◆ Medication can be used to treat the symptoms of edema, if needed.

Radiation Fast Facts

4 Brain Talk, Volume 7, Number 2

IMRTContinued from page 3

words of the acronym—intensi tymodulated. The intensities of the ra-diation beams are non-uniform andthese beam intensities are optimizedto provide solutions that are superiorto what is possible with 3D CRT. Thisfurther complexity needs to be intro-duced into the delivery of the radia-t ion beams, and just as theintroduction of wedges, lead blocksand compensators were a boon for anearlier generation, but not withoutrisk, this further complexity requiredfor IMRT is a double-edged sword forpatients and physicians.

The intensity of every radiationbeam is deliberately and purposefullymodified during the time that the radi-ation is delivered. Conceptually, eachbeam is broken up into little “beam-lets.” During the time that a portal isbeing treated, some areas are given alot of radiation while adjacent areasare given very little radiation. This ismost commonly achieved by using acomputer to control the position of anumber of beam shaping devices (apair for each beamlet).

As these devices, called multileafcollimators or MLCs, are moved intothe radiation beam from the edges ofthe field, the intensity of the radiationthat is being delivered to the patientfrom that beamlet is decreased.Leaving them open through an entiretreatment gives the highest intensity,and having them closed throughoutgives the lowest intensity radiation tothose segments. Some portals maynot be used for irradiating the entiretumor, but will just use several beam-lets to supplement the dose being de-l ivered by the other portals . Thetreatment machine is on longer andgenerates more X-rays when deliver-ing IMRT. Many of these X-rays arenot used, because of the need to blockmany of them out while giving thelast bit of radiation to the areas thathave been prescribed the beamletswith the highest intensity.

The sum of the radiation given byeach of these intensity modulated ra-diation beams is the dose that is deliv-ered to the patient. It is possible withIMRT to design concave target dosedistributions and to specifically pro-tect normal tissues which are sensi-tive to radiation.

There are differences in the unifor-

Continued on page 10

‘Gray’ and ‘centiGray’ are units of measurement for radiation treatment

Radiat ion is measured by theamount of energy absorbed by thebody. The unit of measurement is theGray, abbreviated Gy. The term Grayreplaced an older term, rad. Other unitsof measurement are the centiGray(cGy) and the rad. One cGy equals onerad. Thus one Gray equals 100 cGy or100 rad. The average X-ray used for di-agnosis exposes a person to about.0072 cGy.

Radiation used to treat brain tumorsin conventional radiation therapy in thepast was about 6000 cGy or 60 Gy.

Today, new research is showing that 3000cGy or 30 Gy received over a period of 10sessions may be as effective as the larger60 cGy received over a period of 30 or sosessions. While these doses may seemhigh, they are spread over a relativelylarge target region.

With one session of sterotactic radio-surgery, the radiation dosage can rangefrom very small (15 Gy) to very large (70Gy). The dosage is a function of the typeof tumor or lesion being treated and theeffect that is desired.

diation during its delivery have variedas well . Technical l imitat ions ofmany of these solutions have prevent-ed them from being commonly ac-cepted and used.

Nearly every company that is con-cerned with radiotherapy treatmentplanning software has realized the im-portance of IMRT for the field of radi-ation oncology, and has developed oris developing products that allow theplanning and delivery of IMRT treat-ments. These companies includeMDS Nordion (http://www.mdsnor-dion.com), Philips Medical Systems(http://www.medical.philips.com/product_lines/adac/products/rtp/p3_imrt/ index.asp) and Siemens MedicalSystems (http://siemensmedical.com)

These companies and the compa-nies listed below have similar goals.All are attempting to develop prod-ucts and services that will help pro-vide a seamless l ink betweenimaging, planning, and treatment forcomplex oncologic indications. Theuse of communication standards hasfacilitated the development of theseseamless l inks between equipmentprovided by different manufacturers.

Serial and Helical TomotherapyThe most commonly used IMRT

delivery technique to date has usedsoftware and hardware equipment de-veloped by the NOMOS corporation(http://www.nomos.com). This pioneer-ing technology uses serial tomothera-py ( l i teral ly “sl ice therapy” arcsdelivered by a special collimator (abeam shaping device) that is attachedto a standard medical linear accelera-tor). Great care must be taken to en-sure that each adjacent arc (or slice)

mity of the dose of radiation to thetumor and to the normal tissues thatare much greater than were previouslytolerated. In order to get the 3D doseof radiation to be shaped very closelyto the tumor (with low doses of radia-tion to adjacent tissues) there may behot spots that receive 10 – 20% moreradiation than the rest of the tumor.

Avoiding having these hot spotswhile still avoiding treating adjacentnormal tissues beyond their tolerancemay mean that parts of the tumor willnot receive the full dose of radiationprescribed! If the treatment of atumor includes normal tissues withina hot spot (i.e., if the tumor has infil-trated normal tissues that need to betreated as well), the normal tissuesmay not be able to tolerate receiving ahigher dose of radiation, and theremay be increased complications thatdevelop after the treatment is com-pleted.

It is significantly more complex tomonitor and measure the amount ofradiation that is being delivered viamany small beamlets than throughfields that are relatively uniform insize and shape and radiation intensity.Radiation exposures outside the areabeing irradiated can be higher be-cause of leakage of radiation from thetreatment machine during the longertimes that the beam is on.

Some radiat ion therapy depart-ments do not have adequate shieldingfor the rooms that the treatment ma-chines are in to allow IMRT to be de-l ivered in those rooms—peopleworking in adjacent areas outside thetreatment room could be receivingunacceptable doses of radiation.

The solutions developed for actual-ly modifying the intensities of the ra-

Grace , 48 , i s ahappy woman .She’s about to be-come a g r and -mother.

Her first grand-child will be a boy.“They’ve a l r eady

picked the name,” she says of herdaughter and son-in-law, “but theywon’t tell us. They want to have asurprise for their parents.”

“I feel like I’ve been fortunate,”she says. Seven years ago, Gracelearned she had breast cancer. “Ifound a lump in my left breast, andmentioned it to my dermatologist,”she r eca l l s . “The de rma to log i s tsent me to a surgeon, who sent mefor a biopsy.” The results showedthat the lump was benign.

But about s ix months later, shefound another lump. This time theb iopsy showed i t was cancerous ,and Grace had a lumpectomy.

“ I wen t t o t he doc to r s eve rythree months a f te r the lumpec to-my,” she says. “After about a year,there was another tumor in the sameplace where I had the lumpectomy.”Grace had a mastectomy, and then,reconstructive surgery.

After a year or so had passed, shedeve loped a cough . “My f ami lydoctor treated it as a cold,” she re-calls. Later, he sent her for a chestX-ray. The cancer had spread toher lungs.

Grace thought to herse l f , “Jus ttell me what to do and let’s get onwith it .” She began chemotherapy.“I took Taxol and another drug forabout seven months,” she says.

After the treatments, “The doc-tors wanted to know if I was a can-didate for s tem cel l surgery,” sheremembers. “When I was comingto the end of the Taxol t reatment,my oncologist recommended anoth-er doctor who was doing stem celltreatments. That’s when they foundthe lesions on the brain.”

5Brain Talk, Volume 7, Number 2

Grace and daughters, Lauren & Jennifer

Living with Metastatic Breast Cancer

In 2000 and ear ly 2001 , Gracehad three Gamma Knife surgeries atYa l e -New Haven Hea l t h GammaKni fe Cen te r in New Haven , CT.“It’s wonderful, it’s a great proce-dure,” she says.

Her l as t Gamma Kni fe surgerywas one year ago. Since then, shehasn ’ t had any new b ra in me ta s -t a ses . “There ’s c loud ing a roundthe o ld t umor, ” she r epo r t s . “ Idon’t know if it’s radiation damageor growth.”

“Thank heavens for the GammaKnife ,” she says. “I’ve just beenable to get on with my life. I have avery, very active social life.”

“I feel wonderful—there are mo-men t s when I don ’ t , l i k e when Ihave colds or an abscessed tooth,”she explains. “This past year I hadan absce s sed t oo th and my f aceswelled up. They weren’t sure if itwas cance r. I t was such a r e l i e fwhen i t t u rned ou t t o be an ab -scessed tooth.”

Late las t summer, “They saw atumor in the breastbone area in oneo f my CT scans , ” Grace s ays .Navalbene was added to her treat-ment regimen for s ix months. “I tmade my hair thin out,” she states.“But in my most recent CT scan thetumor was gone,” she says happily.

“ I have He rcep t i n t r e a tmen t seve ry week , ” she r epo r t s . “ I ’vebeen on Herceptin for the last threeyears. I’ll continue taking it indef-

initely.” Herceptin is a monoclonalantibody that attaches to a growthfac to r r e cep to r on b r ea s t c ance rce l l s , p r even t i ng g rowth f ac to rmolecules from attaching.

“ I f I d idn ’ t have t o go eve ryFriday, I wouldn’t know that I wastaking it,” she says of the Herceptintreatments. “Where I go for treat-ment, i t’s l ike a social thing,” sheadds.

Grace has two daughters . “Myyoungest, Lauren, was just marriedto Rob in February,” she says lov-ingly. “Jennifer and my son-in-lawDave are about to have a baby. Myfamily’s growing, i t’s wonderful.”He r f ami ly a l so ha s two boxe r s ,which are large-breed dogs.

Grace works in the shipping of-f ice of a company tha t overhaulsand r epa i r s he l i cop t e r s . “Some[he l i cop t e r ] pa r t s wen t t oAfghanis tan,” she says . “When Ihea r abou t a sh ip ove r nea rAfghan i s t an , I c an s ay I r ou t edparts to that ship.”

In addition to staying busy withher family and work, “I have a lotof girlfriends I go out with,” Gracesays . “And I love to read, I readconstantly.”

“ I f ee l p re t ty good abou t eachday,” she says.“The only limitation to tomorrow

is our doubts of today.”~ Unknown

6 Brain Talk, Volume 7, Number 2

Stereotactic Body Frame

Stereotactic Radioablation

Areas where Radioablation and IMRT may be helpful...◆ To eliminate stray cancer cells.

◆ After surgery for benign or malignant tumors to stop the growth of any residual tumor.

◆ To stop the spread of body cancers to other parts of the body.

◆ To relieve symptoms by shrinking tumors.

◆ Where tumors are considered inoperable.

◆ To shrink the tumor so that surgery can be performed.

Focusing Damage toward Tumors andaway from Healthy Tissues Using Extra-

cranial Stereotactic Radioablation

Radiosurgery was a term coinedby t he r enowned neu rosu rgeon ,Professor Lars Leksell, to describea special single-session high-doseradiation treatment where multiplehighly focused and extremely pre-cise beams of radiation convergedon a t a rge t . Thes e r ad io su rge rysessions were very different fromthe ma ins t r eam o f r ad io the r apytrea tment where the to ta l dose ofradiation was divided up into manysma l l packe t s ( f r a c t i ons ) g ivendaily over many weeks.

The radiosurgery treatment wasintended to be disabling to targetedt i s sue s ( e . g . t umor s o r va scu l a rma l fo rma t ions ) wh i l e go ing t ogreat lengths to avoid dose to nor-mal tissue.

In con t r a s t , t h e conven t i ona lf rac t iona ted rad ia t ion t rea tmentsexp lo i t ed t he g r ea t e r ab i l i t y o fhea l t hy t i s sue t o hea l r ad i a t i ondamage caused by smal l doses ascompared to tumor t i s sue . Af te rall, tumor cells use the majority oftheir resources to divide while nor-mal tissues must have the capacityto heal the damage of everyday life.

This convent ional f rac t ionatedradia t ion t reatment was of ten notvery accurate or precise with largevolumes of normal tissue being ex-posed t o t r e a tmen t dose s .Howeve r, t he f r a c t i ona t i on wassomewhat “forgiving” of this inno-cent exposure.

As one could predict, eventuallythe r e c ame a hyb r id app roachcalled fractionated stereotactic ra-d io the rapy in wh ich componen t srespons ib le fo r the accuracy andp rec i s i on o f r ad io su rge ry we recombined wi th the normal t i s suesparing of conventional fractionat-ed radiotherapy. All of these treat-ment paradigms have found a placein the arsenal doctors use to t reatdisorders of the brain.

Both s t e reo tac t i c r ad iosurgeryand stereotactic radiotherapy havespecial limitations when used in thebrain. The brain itself is one of themost poorly tolerant structures to-wa rd r ad i a t i on i n t he body.Damage to the brain from radiationcan be catastrophic.

If even a small part of the braini s s i gn i f i c an t l y damaged by t hetreatment, it is unlikely that anoth-er undamaged part of the brain willbe able to take over the task. Theseinherent problems wi th to leranceimpose s eve re r e s t r a i n t s on t heconduc t o f s t e reo tac t i c r ad ia t iontreatments to the brain . As such,larger tumors are typically treatedwith smaller doses. This is not in-herently desirable since larger tu-mors actually require higher dosesto control growth. Nonetheless, itis a direct consequence of the radi-ation tolerance of the normal func-tioning brain.

In the ear ly 1990s , researchersf rom the Ka ro l i n ska Hosp i t a l i nStockholm, Sweden, began stereo-tact ic t reatments in the body (ex-tracranial sites). They developed a

special frame, called the stereotac-t ic body frame, to immobil ize thepatients, decrease respiratory mo-tion, and facilitate the stereotactictargeting.

Other groups in Europe, Japan,and t he Un i t ed S t a t e s e i t he r a c -quired this Swedish technology ordesigned their own systems to con-duct extracranial stereotactic treat-ments. During this period, greatervo lumes o f c l i n i ca l expe r i encehave been acquired and describedin journal publications. Typically,these treatments were delivered inmore than one session with modestto high doses per treatment.

S ince there was more than onet r ea tmen t and accu racy was no tsubmi l l ime t e r, t he se new t r ea t -men t s cou ld no t be ca l l ed r ad io -surgery. As such they were initiallytermed extracranial stereotactic ra-d io the r apy. Pub l i c a t i ons f romSweden, Germany, and Japan havea l r eady demons t r a t ed t ha t t he senew treatments are quite effectiveat stopping the growth of liver andlung me ta s t a se s w i th accep t ab l etoxicity.

Our group at Indiana Universityperformed our first high-dose lungtreatments (≥1000 cGy per fractionfor up to three f ract ions) in 1994under the d i rec t ion of Dr. JosephMontebello, using the tip of a bron-

Continued on page 7

7Brain Talk, Volume 7, Number 2

Dr. Robert Timmerman

RadioablationContinued from page 6

choscope abut t ing the tumor as af i duc i a l . These t r ea tmen t s we redramatically refined in early 1997with the acquisit ion of the stereo-t ac t i c body f r ame deve loped i nSweden. Initially, we treated lungand l iver metas tases wi th s imi lardose p resc r ip t ions and dose p ro -files as the Karolinska group.

Even tua l l y, t hough , we beganformal tes t ing to “push the enve-lope” of dose by conduct ing doseescalation protocols. These studiesa r e common in t he r ea lm o fchemotherapy. I t is assumed thatcancer is a tough competitor, typi-cally surviving despite the damagecaused by any treatment. As such,the highest dose tolerated of a par-ticular therapy is ideally the rightdose to use in all patients. In orderto determine this highest dose, alsocalled the maximum tolerated dose(MTD) , pa t i en t s a r e t r e a t ed i ngroups with the same dose.

If the majority of patients toler-ate a part icular level without s ig-n i f i c an t t ox i c i t y, t he dose i si nc r ea sed modes t l y f o r t he nex tg roup . The p roce s s i s r epea t eduntil the treatment is no longer welltolerated. The highest dose tolerat-ed is deemed the MTD, and all fu-t u r e t r e a tmen t s a r e g iven a t t ha tlevel.

We have r ecen t l y comple t ed adose escalation trial in early stagelung cancer for medically inopera-ble patients. This is a population ofpat ients with many medical prob-l ems , t yp i ca l l y t obacco - r e l a t ed ,who a r e f ound t o have a l im i t edlung cancer that has no evidence ofspread to lymph nodes o r d i s tan ts i t es . Surg ica l the rapy for thesepatients would offer hope of cure ina round 70%. Unfo r tuna t e ly, t heon ly ava i l ab le a l t e rna t ives , con-ventional fractionated radiation orchemothe rapy, have much l owercure rates.

The results of this trial, soon tobe published, have been surprisingand encourag ing . The MTD wasnever reached despi te seven doseescalat ions to 2000 cGy per f rac-tion times three fractions. Lung tu-mor s t r e a t ed a t t he h ighe r dose sseem to be controlled, although thefollow-up is short. Most interest-

ingly, the toxicity of the treatmentin such a f ra i l pa t ient popula t ionhas been very low.

A few pat ients had a decl ine inpulmonary function, but the major-i ty have had no i l l e ff ec t s . Th i shigher tolerance of radiat ion thanobserved in the brain is probably aconsequence of the differences infunctional architecture between thetwo o rgans . Wh i l e t he b r a in i scomposed of specific regions per-fo rming d i f f e r en t spec i f i c f unc -t i ons , t he l ung i s composed o flarger regions a l l doing bas ical lythe same task (exchanging oxygenbe tween t he a i r and t he b lood -stream). Apparently if a small re-g ion o f t he l ung i s damaged bytreatment, the rest of the lung tis-sue makes up for the loss of func-tion, even in people with inherentlung disease.

The results of this dose escala-t ion t r ia l have genera ted in te res tf rom many s i t e s i n t he U .S .Another t r ia l in the same popula-tion is being developed through theRad i a t i on The rapy Onco logyGroup , a coopera t ive consor t iumfunded by t he Na t i ona l Cance rIn s t i t u t e , wh ich w i l l u se t heIndiana University trial as the basisfor dose select ion. Other inst i tu-t ions, including Thomas JeffersonUniversity, University of Colorado,C leve l and C l in i c , Wake Fo re s tUniversity, Washington University,Un ive r s i t y o f Ca l i f o rn i a a t SanFranc i s co , Un ive r s i t y o fPennsylvania, St. Louis University,Lee Moffitt Cancer Center, MedicalCo l l ege o f Wiscons in , andUniversity of Wisconsin plan trialsfo r va r ious s i t e s in the body andvarious indications.

The Indiana University dose es-ca la t ion t r i a l s demons t ra t ed tha tthe tolerance of cer ta in organs inthe body (e .g . lung and l iver) farexceeds the tolerance of the brain.As such, much higher doses of radi-ation can be delivered to extracra-nial sites, even with somewhat lessaccurate technologies , than couldbe delivered in brain radiosurgery.In fact , the t reatment in the bodyhas become “ablative” or destruc-tive with little likelihood of cellu-lar viability within the target aftertreatment.

Along this line, we have renamedthese ve ry h igh -dose t r e a tmen t sou t s i de t he b r a in “ex t r ac r an i a l

stereotactic radioablation” or ESR.The ESR treatment includes opt i -mal immobilization, efforts to de-c r ea se o rgan and r e sp i r a to rymotion, s tereotact ic target ing andtreatment del ivery, and very highfocal dose treatments. SuccessfulESR requires that the target be lo-cal ized and demarcated, that onlytumor is targeted ( i .e . no prophy-lactic treatment), and that the dosebe very limited to the target i tselfwith rapid falloff to normal tissue.

As resu l t s a re publ i shed , moreand more centers wil l acquire thecapability for ESR. ESR is unusualin the high technology realm of ra-diation treatment in that it requiresmore specialized training of physi-c i ans and phys i c i s t s r a t he r t hanspecialized equipment.

Ideally, pat ients receiving suchtreatments will be enrolled in for-mal protocols. ESR has the poten-tial to dramatically change the waysevera l common presen ta t ions ofcancer a re t rea ted . Wi th prudentinvestigation, research, and scruti-ny of published reports, hopefullythis new therapeutic paradigm willmake an impac t on cance r i n t hebody on t he o rde r o f t he impac tmade by radiosurgery in the brain.

.

8 Brain Talk, Volume 7, Number 2

Dr. Joseph Landolfi

What Is a Neuro-Oncologist?This is a question often asked by

pa t i en t s who come to my o ff i c e .Some t imes peop l e a r e awa re o ftheir diagnosis and believe I mustbe s ee ing t hem fo r t he i r t umor,whi le others are unaware of thei rdiagnosis and fear the term and theidea of oncology or cancer. The of-ficial definition: Neuro-oncology isa medical discipline that deals withthe d iagnosis and t rea tment of 1)metastatic and non-metastatic neu-rological complicat ions of canceroriginating outside of the nervoussys tem (e .g . , b reas t cance r, l ungcancer, melanoma, etc.), 2) primarycentral nervous system neoplasms(gl iomas, meningiomas, e tc . ) and3) pain associated with cancer.

Gene ra l l y, a neu ro -onco log i s t(brain tumor doctor) takes care ofpatients with brain tumors or spinalco rd t umor s . Spec i f i c a l l y, weguide patient care. For instance, ifa patient were sent to me for evalu-ation of a brain lesion, I would takea history and examine the patient. Iwould rev iew a l l the X-rays ( i . e .CT /MRI ) t o de t e rmine i f t he l e -sion/mass is a tumor or somethingelse.

I f i t we re a t umor d i agnosedsomewhere e l se , I would reques tthe actual pathology slides for re-v i ew by my neu ropa tho log i s t ( adoctor who specializes in brain tis-sue) for confirmation of diagnosisprior to treatment. Once it is estab-lished that a mass may be a tumor, I( the neuro-oncologis t ) make rec-ommendations in consultation witha neu rosu rgeon on how to de t e r -mine the type of tumor. This maybe a biopsy or removal of the tumorwhen safe.

Sometimes i t is possible to tel ljust from the MRI, but only for cer-ta in types of tumors. The role ofthe neuro-oncologist is to help thepatient choose a neurosurgeon withexpe r i ence i n ope ra t i ng on andtreating brain tumors. This wouldbe a pe r son I work c lo se ly w i th ,whom I t rust , that can establ ish agood rapport with my patient. Ford i agnos i s ou r neu ropa tho log i s twould review the specimens fromthe tumor, after biopsy or surgery.

O n c e a d i a g n o s i s i s m a d e , t h e

neu ro -onco log i s t w i l l gu ide t henex t cou r se o f t r e a tmen t , wh ichmay include observation, radiation,chemothe rapy o r a comb ina t i onthereof. Depending on the tumor,the order in which these are givenmay be different. It is the job of theneu ro -onco log i s t t o know whenthese t reatments should be given,how they shou ld be g iven and towhom they should be given. Withregard to radiation, this would be inconsultation with a radiation oncol-ogist (a doctor who treats patientsw i th r ad i a t i on fo r va r i ous d i s -eases). Again, this would be some-one I t r u s t who ha s a l o t o fexper ience t rea t ing pa t ien ts wi thbrain or spinal cord tumors.

Fo r p r ima ry b r a in t umor s ,chemotherapy is chosen and admin-istered by the neuro-oncologist andhis or her staff. For metastatic tu-mors that spread to the brain (e.g.f r om b rea s t , l ung , co lon , e t c . )chemotherapy i s adminis te red bythe med ica l onco log i s t w i th t heneu ro -onco log i s t c a r i ng fo r t hebrain disease. The neuro-oncolo-g i s t wou ld mon i to r t he pa t i en t ’slaboratory results, physical exami-nat ion and, of course, the MRI orother X-rays.

The neuro-oncologist decides ifa treatment is working and when itis not working, and when the timehas come to change t r e a tmen t s .They are also aware of various clin-ica l t r ia l s , or exper imenta l t rea t -men t s , t ha t may be ava i l ab l ewor ldwide fo r t he i r pa t i en t s andwhen such therapies should be con-sidered. We can be a patients’ re-sou rce fo r i n fo rma t ion andtreatment. We are also there to ex-plain information they may find onthe i r own—from o the r doc to r s ,o the r pa t i en t s , f ami ly, f r i ends ,books, or the Internet.

The neurosurgeons I work withlike to describe me to the patientsas “the captain of the ship”—work-ing together with a team to guidepatient care and treatment. As thecaptain, i t is my responsibi l i ty tosee that each patient is offered thebest treatment available, most oftenindividually tailored for his or herspecific tumor and needs.

A t ou r i n s t i t u t i on , t he t e ammeets once a week to d iscuss pa-t ien t cases and t rea tment . Alongwith nurses and support structuresin place for specific needs, we alsoprovide support to the patient andtheir families. Also available na-t i onwide a r e suppo r t g roups o fo ther pa t ien t s suffe r ing f rom thesame disease. In my area the sup-po r t g roup i s r un by one o f t heIns t i t u t e s ’ neu rosu rg i ca l nu r se s ,Patty Anthony, R.N. This providesan added bene f i t t o t he pa t i en t sseen statewide.

Why Do We Need Neuro-Oncology?A neuro-oncologis t can be any

physician who completes a formalfel lowship (post-residency) t rain-ing program in the f ield at one ofthe approved p rograms ava i l ab lenat ionwide. In some faci l i t ies , i tmay be a medical oncologist withspecial interest in the area but whohas no t been fo rma l ly t r a i ned .Personally, I feel a neuro-oncologyfe l l owsh ip - t r a ined phys i c i an , i nparticular a neurologist, best servesthe pa t i en t s . As we have s eenthrough recent evidence, the ner-vous system and cancer are biologi-ca l l y l i nked . A neu ro log i s t i strained in understanding the intri-c a t e r e l a t i onsh ip o f t he ne rvoussystem to the rest of the body, andthrough formal t ra ining in neuro-oncology develops an understand-ing o f t he ne rvous sy s t em a s i trelates to cancer. This knowledge

Continued on page 9

9Brain Talk, Volume 7, Number 2

Neuro-OncologistContinued from page 8

is an integral part of the diagnosisand management of pa t ien ts wi ththese disorders.

For example, there are disordersknown as paraneoplastic syndromesin which a patient with a systemiccancer will develop an immune re-action against the nervous system.This is because of a foreign proteinor antigen on the cancer cell that issimilar to a protein found on cellsin t he ne rvous sys t em. Th i s im-mune response can cause neurolog-i ca l s i gns and symp toms o f ava r i e ty o f p r e sen t a t i ons r ang ingfrom muscle weakness to imbalanceto confusion. In a large number ofcases, these signs may be seen evenbefore the discovery of the cancer.An unders tanding of these d i sor -ders and an awareness of their exis-t ence a id i n e a r l y d i agnos i s andmanagement of these patients andtheir diseases.

Neu ro -onco logy p rob l ems a r ecommon but unique because of theunique anatomy and physiology ofthe nervous system. In an issue oncancer s ta t i s t ics by the AmericanCancer Society (2000), it was esti-mated that there would be a total of1,220,100 new cancer cases annual-ly in the USA, wi th 16 ,500 casesor ig ina t ing f rom the cen t ra l ne r -vous system. This number is an es-t ima t e a s no t a l l s t a t e s have acancer registry. This number doesnot include the neurological com-

plications of cancer and i ts thera-pies including but not limited to theside effects of chemotherapy, radia-t ion and surgery. I t also does notinclude indirect compl icat ions ofcancer such as s t roke , in fec t ionsand paraneoplastic syndromes. Theda t a f r om 1998 sugges t an i nc i -dence rate for all primary brain tu-mor s o f 11 .8 pe r 100 ,000person-years. The number of brainmetastases is estimated to be in therange of 97,800-170,000 new casesannually.

Neuro-oncology is a highly spe-c ia l i zed f ie ld requ i r ing a t ra inedphys i c i an w i th expe r t i s e andknowledge in recognizing the largenumber of disorders and their ther-ap ies . There a re approximate ly acouple of hundred of us nationwideand the field is growing. Throughthe e f fo r t s o f t he se i nd iv idua l s ,g r ea t s t r i de s have been made i ntreating this disease. For myself, itis a f ield of personal satisfaction.Many colleagues, patients and theirfamilies see this profession as dif-ficult because of the nature of thedisease. I always reply that I prac-t ice wi th compass ion in my hear tand a sense of humor in my deliv-ery. Quality of life and comfort areas important, if not more important,than quantity of life to many of mypatients.

I hope t h i s b r i e f a r t i c l e he lp sclar ify the important role and ne-ce s s i t y o f t he neu ro -onco log i s t .Above is an incomplete list of someof t he d i s ea se s c a r ed fo r by aneuro-oncologist.

Primary Brain Tumors:◆ Glioblastoma multiformes◆ Low grade and anaplastic

astrocytomas/oligodendrogliomas◆ Pilocytic astrocytomas◆ Pleomorphic xanthoastrocytomas◆ Brainstem gliomas◆ Meningiomas◆ Ependymomas◆ Gangliogliomas◆ Acoustic and other neuromas◆ Pituitary adenomas◆ Primitive neuroectodermal tumors◆ Medulloblastomas◆ Neurocytomas◆ Atypical rhabdoid teratoid tumors

Direct Complications of Cancerfrom:◆ Lung cancers◆ Breast cancers◆ Melanomas◆ Colon cancers◆ Other systemic cancers

Diseases spread to the:◆ Brain◆ Spinal cord◆ Leptomeninges◆ Nerves◆ Muscles

Indirect Complications of Cancer:◆ Vascular disorders◆ Metabolic disorders◆ Nutritional disorders◆ Coagulopathies (blood disorders)◆ Paraneoplastic disorders

Side Effects from Surgery, Radiation and Chemotherapy:◆ Stroke◆ Infections◆ Neuropathies◆ Encephalopathies

22-Year SurvivorContinued from page 2

cord and I have a painful weak leg.More consultations with special-

i s t s i n neu rosu rge ry and r ad io -surgery have led me to the decisionto try another technology that maywork on the spine well , called theCyberKnife. My doctor said therei s a r i sk o f pa r t i a l pa r a ly s i s andcons t an t pa in t ha t m igh t shoo tdown my leg, but after weighing allthe risks, my doctors and I feel thatth is wi l l g ive me the bes t chancefor survival and mobility.

If this was even five years ago, Iwould be in deeper trouble riskinga dangerous spinal surgery. I amgra t e fu l f o r t he who le f i e l d o fstereotactic radiosurgery and radio-therapy. I am 48 years old and havetwo minor children at home, and Ineed to do whatever I can, risky ornot , to preserve my eyesight , mo-bility, and my life. I will send in anupdate after the procedure!!! Wishme good luck!

Diseases a Neuro-Oncologist May Be Helpful with...

10 Brain Talk, Volume 7, Number 2

IMRTContinued from page 4

neither overlaps nor underlaps i tsneighbors, or there may be too muchor too l i t t le radiat ion delivered tosome tissues.

A modification of serial tomothera-py is helical tomotherapy. The helixis described by the continuous linearmovement of the treatment couchthrough a rotating 6 MV linear accel-erator gantry. A collimator similar tothe one used by the NOMOS device isused to temporally modulate the in-tensity of the X-ray beam as it treatsthe patient. The technology for theprototype device was developed at theUniversity of Wisconsin in Madisonby a consort ium between theUniversity and industrial partners.

The further development and mar-keting of this device is being carriedout by TomoTherapy, Inc. (http://www.to-motherapy.com), which has received510k clearance (Food and DrugAdministration approval to marketthe device for the medical indicationsrequested) for marketing a helical to-motherapy device in the United Statesof America.

Dynamic Multi Leaf Collimator IMRTAn increasingly commonly used

method of delivering IMRT involvesconventional MLCs on conventionalmedical l inear accelerators. Thistechnology is relatively common, buta great deal of additional quality as-surance testing must be performed toensure that this equipment is accurateand reproducible for its use in deliv-ering IMRT. Each pair of MLCleaflets is independently swept acrosseach radiotherapy portal under com-puter control while the beam is on.The speed of the motion of the lead-ing leaflet and the trailing leaflet willdetermine the length of time that anygiven area is irradiated, and will thusdetermine the intensity of the radia-tion delivered to that portion of thatradiotherapy portal.

This type of IMRT can be adminis-tered either with the linear acceleratorgantry moving around the patient orwith the gantry in a stable position.This form of IMRT was first imple-mented at Memorial Sloan-KetteringCancer Center and is called DynamicMulti Leaf Collimator (DMLC) IMRT,or more simply, DMLC. Commercialsoftware capable of delivering DMLCis offered by Varian Medical Systems,Inc. (http://www.varian.com),Elekta

(http://www.elekta.com) and BrainLAB(http://www.brainlab.com).

The quality assurance required forensuring that treatment is being deliv-ered as prescribed while the MLCleaflets (and possibly the gantry) aremoving is significant. The more mov-ing parts that need to be monitoredwhile treatment is being delivered,the greater the chance for error i fthings are not calibrated accuratelyand working within very close toler-ances.

Segmental Multi Leaf Collimator IMRTThere is another method of deliver-

ing IMRT with a conventional MLCwhich does not have the gantry mov-ing while the X-ray beam is on. TheX-ray beam is also turned off whilethe MLC leaflets are moving. In thisform of IMRT, treatment is deliveredonly when the leaflets have reachedcertain prescribed positions, and thishas been termed “step and shoot”therapy. A more formal name is seg-mental MLC (SMLC) IMRT, or moresimply, SMLC. This is perhaps themost common form of IMRT beingadministered currently, as it is some-what easier to perform the requisitequality assurance checks on this typeof IMRT. Many vendors’ softwarewill support planning and delivery ofstep and shoot IMRT.

Image-Guided IMRTA completely different approach to

IMRT was developed by a group atStanford University, which mounted asmall linear accelerator on an indus-trial robot (http://www.accuray.com).Tiny beamlets can be aimed by thisdevice at a tumor from virtually anyposition about the patient, providinggreater flexibility than other methodsof delivering conformal dose distribu-tions.

This concept was initially testedfor stereotactic radiosurgery, and theequipment has received FDA clear-ance for radiosurgical treatment of tu-mors anywhere in the body. Smallnumbers of patients have been treatedwith several fract ions using thisequipment for tumors that are withinimportant organs like the lung or thatare close to or involving cri t icalstructures such as the spinal cord.

SummaryThe ability of IMRT to decrease the

dose of radiation to normal tissues hasled some physicians to use IMRT toincrease the daily dose to the tumorwhile keeping the dose to normal tis-sues the same as could be achieved

with 3D CRT. This can deliver agreater dose of radiation to the tumorwhile not exceeding the tolerance ofthe normal tissues. It is conceivablethat a course of curative radiotherapycould be shortened through this ap-proach without changing an accept-able level of side effects. Similarly, acourse of treatment may be given overthe usual period of time, with a lowerlikelihood of side effects to the nor-mal tissues that would otherwise suf-fer adverse effects from the treatment.

One final thing must be empha-sized about IMRT. The irradiationtechniques require high gradients ofdose in individual radiation portals,and a higher level of precision is re-quired in all steps of the planning anddelivery of treatment. No matter howprecisely a treatment can be plannedand how good it looks on a computerscreen, it is known that there will bedaily changes in the accuracy of thepositioning of the patient for treat-ment, of the location of the tumorwithin the patient, and of normal or-gans that are supposed to be protectedfrom the radiation. During the courseof treatment, these changes in the po-sitions of normal tissues and of thetumor will result in differences be-tween the dose of radiation given andwhat was prescribed.

Attempts are being made to devel-op techniques that will help track theposition of the tumor and of the criti-cal normal tissues during a course oftherapy. These include the use ofdaily ul trasound examinations toguide patient positioning treatment,the placement of tiny metal markerswithin the tumor that can be seen onX-ray pictures, and even daily CTscanning! The level of enthusiasm forIMRT is high, and its promise is great.There are still many technical chal-lenges that need to be addressed tomake intensity modulated radiationtreatments as safe, easy, and repro-ducible as we can imagine thembeing. It is easy to predict that asIMRT gets better and better, it will bemore and more commonly used totreat tumors with curative doses of ra-diation while minimizing side effectsto normal tissues.

11Brain Talk, Volume 7, Number 2

Radiation InjuryContinued from page 12

The International Radiosurgery SupportAssociation is an independent organiza-tion dedicated to providing informationthrough personal contact and educationalmaterials, encouraging research and pro-moting patient options about radiosurgerytreatment and its availability.

❦ Rebecca L. EmerickManaging Director

❦ T. K. LedbetterEditor

❦ Tomasz HelenowskiMedical-Technical AdvisorChicago, IL USA

BRAIN TALK (ISSN 1086-427X),IRSA’s support publication, is publishedquarterly by the InternationalRadiosurgery Support Association.Business office located in Harrisburg,PA. Contents copyright 2002 by IRSA.All rights reserved. Call (+717) 671-1701for information.

DisclaimerThis publication is not intended as a

substitute for professional medical adviceand does not address specific treatmentsor conditions specific to any patient. Allhealth and treatment decisions must bemade in consultation with yourphysician(s), utilizing your specificmedical information.

❦ Alan AppleyLafayette, LA USA

❦ Ronald BrismanNew York, NY USA

❦ Lawrence ChinBaltimore, MD USA

❦ David CunninghamMemphis, TN USA

❦ Alain C de LotbinièreNew Haven, CT USA

❦ Christopher DumaNewport Beach, CA USA

❦ Michael S. EdwardsSacramento, CA USA

❦ Maheep Singh GaurNew Delhi, India

❦ Jordan GrabelWest Palm Beach, FL USA

❦ Deane JacquesLos Angeles, CA USA

❦ Jonathan KniselyNew Haven, CT USA

❦ Douglas KondziolkaPittsburgh, PA USA

❦ Joseph LandolfiEdison, NJ USA

❦ Edward R. Laws Jr.Charlottesville, VA USA

❦ Christer LindquistLondon, England UK

❦ L. Dade LunsfordPittsburgh, PA USA

❦ Georg NorénProvidence, RI USA

❦ Kenneth OttLa Jolla, CA USA

❦ Edward ShawWinston-Salem, NC USA

❦ Swaid N. SwaidBirmingham, AL USA

❦ Robert TimmermanIndianapolis, IN USA

❦ Harish ThakrarChicago, IL USA

❦ Richard WeinerDallas, TX USA

❦ Aizik L. WolfCoral Gables, FL USA

❦ Ronald YoungLos Angeles, CA USA

Contributing Authors and Medical Advisors:

brain talkVolume 7, Number 2

Combinations of technologies and treatments may be best

In many instances, the best treatment for a malignant tumor or metastasesmay be a combination of many treatment modalities. Recent research suggeststhe best outcomes and best quali ty of l i fe may occur when combinations ofsurgery, radiation therapy (brain and body), stereotactic radiosurgery (brainonly), conformal radiation (brain and body) and chemotherapy are all utilizedor some combination of these are utilized to treat body cancer or brain tumors.Research also suggests that less time between each of these various treatments,depending upon the specific patient’s condition, may provide the best result fora cure or lengthening of life.

treatment to the brain, is now a rec-ognized, al though extremely rare,poss ib le long- te rm s ide e ffec t o fradia t ion to the bra in . I t i s mostoften associated with whole brainradiation or with fractionated radi-a t ion the rapy. Each o f these ap-proaches results in radiat ion doseto more heal thy bra in t i ssue thanone-session radiosurgery.

One-Session RadiosurgeryThe most important determinants

of whether there is radiation injuryto the brain are the volume of braintissue that is targeted and the totaladministered radiation dose.

The volume of targeted brain canbe r educed t h rough t he u se o f ah igh ly con fo rma l r ad io su rge rytreatment plan. This involves uti-l i z a t i on o f mu l t i p l e i nd iv idua lsma l l e r “ sho t s” o f r ad ia t ion tha t“pain t” the tumor wi th radia t ion ,giving as little radiation to the sur-rounding brain t issue as possible.In general, it is easier to administera con fo rma l r ad i a t i on t r e a tmen tplan with a Leksell G a m m a K n i f ec o m p a r e d t o a l i n e a r a c c e l e r a -t o r.

Fractionated Radiation TherapyFractionated radiation therapy is

used to treat brain tumors that aretoo large to treat with one-sessionradiosurgery. As such, a larger vol-ume of normal brain tissue will bei r r ad i a t ed . F r ac t i ona t i ng t r e a t -ment , i .e . giving smaller doses ofradiation (usually 180 – 200 cGy)accumulated over a period of time(usua l l y 5 – 6 weeks o r 25 – 30daily treatments), allows for repair

o f r ad i a t i on - induced damage t onormal b ra in ce l l s . Newer t ech -niques of administering fractionat-ed radiation, such as three-dimensionalconformal radiation therapy and in-tensity modulated radiation therapy,u t i l i ze l inea r acce le ra to r s . Wi th“modern” radiation treatment plan-n ing , t he r i sk o f k i l l i ng no rma lbrain cells (called radiation necro-sis) is about 1 – 5%.

Whole Brain Radiation TherapyBecause ha l f o f pa t i en t s w i th

b ra in me ta s t a se s have mu l t i p l e(two or more) tumors, whole brainradiation therapy (WBRT) is com-mon ly u sed . We now know tha tone - se s s ion s t e r eo t ac t i c r ad io -su rge ry can con t ro l b ra in me tas -t a s e s i n abou t 90% o f pa t i en t s ,whether or not WBRT is given. Inaddi t ion , there i s da ta to sugges tt ha t two- th i rd s o f pa t i en t s w i thbrain metastases will have one, twoor three lesions. Therefore, there isa growing trend in those with 1 – 3me ta s t a se s t o w i thho ld WBRT(whereas WBRT is still “standard”with four or more metastases) , tohopefully avoid the long-term po-tential risks of WBRT.

SummaryEither focused single-session ra-

diosurgery or fractionated radiationtherapy to a larger volume can re-sult in radiation injury to the brain.Careful treatment planning shouldminimize this risk.

Internet: www.IRSA.orgEmail: getinfo@irsa.org

International Radiosurgery Support Association

12 Brain Talk, Volume 7, Number 2

Radiat ion treatments can affecta l l c e l l s t ha t a r e t a rge t ed . Th i smeans when normal heal thy ce l l sa r e unavo idab ly t a rge t ed a longwith tumor cells, there may be in-j u ry t o t he hea l t hy ce l l s . TheMerck Manual states the following:

The nervous system can be dam-aged by radiat ion therapy. Acuteand transient symptoms may devel-op early, but progressive , perma-nen t , and some t imes d i sab l i ngnervous system damage may not ap-pear for months to years. The totalradiat ion dose, s ize of each frac-tion and the volume of brain tissueirradiated all influence the l ikeli-hood of injury. Considerable vari-a t ion in ind iv idual suscept ib i l i t ycompl i ca te s t he e f fo r t t o p red ic tsafe radiation doses. (Source: TheMerck Manua l o f D iagnos i s andTherapy, Sec t ion 14 , Neuro log icDisorders.)

Radiation Injury to the Nervous System

Side e f f ec t s o f r ad i a t i on a r ecaused by the radiation’s effect onnormal brain cells with some beingminimal and reversible and othersbe ing s ign i f ican t and permanent .Additionally, the effects may occurquickly (acute) or months to yearsafter treatment.

Acute reactions occur during orimmediately after radiation. Theyare normal, are caused by swellingand can usually be controlled withco r t i co s t e ro id med ica t i ons l i keDecad ron (dexame thasone ) .Delayed or late reactions are some-t imes pe rmanen t and can be p ro -gressive. They can vary from mildto s eve re and may i nc lude de -creased intellect, short-term memo-ry impai rment , and word- f ind ingproblems and personality changes,among other things. While medicaltreatments are available to help the

symptoms of radiation injury, thereare no known medicat ions to pre-vent or reverse damage.

Oncogenesis, the development ofanother tumor f rom the rad ia t ion

Continued on page 11

Dr. Edward Shaw

Radiation Injury to the Brain