IMRT: Global ViewArno J. Mundt MDProfessor and Chair

Department of Radiation OncologyUniversity of California San Diego, La Jolla CA

A Walk Down Memory Lane

“…further refining of delivery technology and the inverse planningsystem, gaining clinical experience to address target definition and dose inhomogeneity within the targets, and understanding the partial volume effect on normal tissue tolerance are needed for IMRT to excel in the treatment of head and neck cancer….”

TodayIMRT is no longer a “new” or “novel”technologyIMRT has literally “grown up”Pre-IMRT era seems like a long time ago

IMRTA major revolution in our fieldFundamentally changed the way we plan and deliver radiation therapy

IMRT Revolution“There are no non-violent revolutions…”

Malcolm X

Resulted in the upheaval of the daily lives of all of us(physicians and medicalphysicists alike)

IMRT RevolutionProposed over 40 years ago by Takahashi in Japan

Takahashi et al. Acta Radiol 1965;2421st attempted in the late 1960s by Hellman and colleagues (JCRT)Deemed infeasible due to excessive planning and delivery times

IMRT ImplementationIn mid-1990s, IMRT began to be used at select academic centers Not till the late 1990s with the availability of commercial treatment planning systems did IMRT start to become widely availableCurrently, 10 commercial planning systems and 7 commercial delivery systems

BrainLAB (brainlab.com) BrainScanCMS, Inc. (cmsrtp.com) Xio IMRTElekta (elekta.com) PrecisePlanNOMOS (nasmedical.com) CORVUSPhilips (medical.philips.com) Pinnacle-PROProwess Inc (prowess.com) Panther DAORAHD (rahd.com) 3D/Pro, KonradSiemens (siemens.com) KonradTomotherapy (tomotherapy.com) Hi-ArtVarian (varian.com) Eclipse

Commercial Planning Systems

Hamilton et al. Treatment PlanningIMRT: A Clinical Perspective. Mundt A, Roeske J (editors)BC Decker, Toronto, 2005

BrainLAB brainlab.comElekta elekta.comNOMOS nasmedical.comSoutheastern RadiationProducts seradiation.comSiemens siemens.comTomotherapy tomotherapy.comVarian varian.com

Commercial Delivery Systems

Saw C, Ayyangar K, Krishna K, Wu A, Kalnicki SDelivery Systems IMRT: A Clinical Perspective. Mundt A, Roeske J (editors)BC Decker, Toronto, 2005

What is the Current Level of IMRT Use?

IMRT SurveysTwo surveys performed to assess the level of IMRT use in the United States

2002 Survey (450 Radiation Oncologists)Mell LK, Roeske JC, Mundt AJ.Cancer 2003;204-211

2004 Survey (500 Radiation Oncologists)Mell LK, Mehrotra AK, Mundt AJ.Cancer 2005;104:1296-1301

IMRT Surveys

Adoption was at first slow, but later occurred at a very rapid rateIn the 2002 survey, 32% of radiation oncologists were using IMRTIn the 2004 survey, this percentage increased to 74%

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Mell LK, Mundt AJ. Survey of IMRT Use in the USA - 2004 American Radium Society Barcelona Spain 2005

Cumulative IMRT Adoption (USA)

*As of 8/04

IMRT AdoptionInitially only used at a few academic institutions with home-grown systems

With advent of commercially available planning systems, tremendous adoption seen in private practice community

IMRT Utilization Private and Academic Physicians

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IMRT UtilizationWide variety of sites are now being treatedTop 3

Prostate, Head and Neck, CNSIn recent years, increasing interest in other sites

Gynecology, GI, Breast

Site % __Prostate 85% Head and Neck 80%CNS 64%Gynecology 35%Breast 28%GI 26%Sarcoma 20%Lung 22%Pediatrics 16%Lymphoma 12%

IMRT Practice Survey (2004)Top Treated Sites

Mell LK, Mundt AJ. Survey of IMRT Use in the USA- 2004Cancer 2005;104:1296

IMRT UseWhile commonly available, it is being used to treat only a subset of patients at most centers

Rarely used in a large percentage of patients under treatment

IMRT Use

Majority of IMRT users (73%) treat <1/4 of their patients with IMRT<5% use it in >1/2 of their current patients

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Clinical Impressions2004 Survey asked clinical impressions of IMRT usersOverwhelmingly favorableMost only able to comment on acute toxicityFew could comment on chronic toxicity or tumor control

Acute ToxicityMost (87%) felt acute toxicity was similar or better than conventional RT13% felt it was worse (primarily in head/neck cancer*)

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Better Same Worse*many of these also reported ↓acute toxicity in prostate pts

Chronic Toxicity55% could assess chronic toxicityOf these, great majority (73%) felt it was better than standard RTOnly 1 felt it was worseNo 2nd tumors noted (even among long-term users)

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Tumor Control

47% could assess tumor controlOf these, the majority felt it was superior or similarNone felt it was worse

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Future IMRT UseIMRT use will continue to growMajority of current radiation oncology residents are taught IMRTSurvey of Chief Residents at 77 programs → 87% hands on experience>50% planned and treated >25 IMRT ptsWide variety of tumor sites Malik R, Mundt AJ et al.Survey of Resident Education in IMRTTechnol Cancer Res Treat 2005;4:303-309

Site %Head and Neck 92%Prostate 81%CNS Tumors 56%Pediatrics 38%Gynecology 24%Recurrent/Palliative 24%Breast 21%GI 21%Lung 15%Lymphoma 7%

Disease Sites TreatedResident Survey

Why is IMRT so popular????

Cynical Answer

$$$$

Reasons for Adopting IMRT

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*”…don’t all boys love new toys?”

MotivationsFinancial reasons are commonNew billing codes added in 2001 making reimbursement 4 times conventionalIn 2004, reimbursement rates revised down to 2.8 times conventional RT

Financial MotivationsLed some physicians to make false claims about IMRTInternet is full of such misinformation Review of IMRT websites → 42% have false and/or misleading information (including many academic sites!)

Schomas D, Mell LK, Mundt AJ.IMRT and the Internet: Evaluation of Content andQuality of Patient-Oriented InformationCancer 2004;101:412-20

Example StatementsConventional prostate RT can leave the patient

impotent and incontinent…IMRT dramatically decreases these problems

IMRT is a kindler and gentler treatment because it leaves healthy tissues alone

IMRT beams intersect on the tumor by turning corners

The promise of IMRT lies in its ability to focus treatment only on the tumor

Why is IMRT so popular???

Less Cynical ViewImproves sparing of normal tissues, reducing the risk of acute and chronic sequelae → Improving patient quality of life

Improves ability to dose escalate high risk patients, cover of difficult targets and even safely re-irradiate patients →Improving tumor control

And Importantly…..

IMRT rests on an ever growing foundation

of convincing clinical data

IMRT LiteratureInitially devoted exclusively to physics issues, e.g. tongue and groove effect, QA, etc.

Clinical studies have become increasingly common in recent years

IMRT Clinical Studies*

559

364 (65%) 195 (35%) Dosimetric Outcome

*as of 1/1/07

IMRT Clinical Studies

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Clinical Studies

Early Small SeriesVery limited follow-upMostly prostate and head/neck

Larger seriesLonger follow-upWide variety of diseasesites

Every Red J now has IMRT outcome studies

Mackley et al.IMRT for pituitary adenomas: preliminary report of the ClevelandClinic Experience

Daly et al.IMRT for malignancies of the nasal cavity and paranasal sinuses

Bossi et al.IMRT for preoperative posterior abdominal wall irradiation of Retroperitoneal liposarcomas

Lessons from the LiteratureA number of reports highlight various issues/problems/toxicities in IMRT patientsSuch reports improve the quality and delivery of IMRTTeach us how to do IMRT and how not to do it

Mundens et al. (MD Anderson)Radiation Injury to the liver after IMRT in patientswith mesothelioma: An unusual CT appearanceAJR 2005;184:1091-5

Lee N et al. (UCSF)Skin toxicity due to IMRT for head/neck cancerInt J Radiat Oncol Biol Phys 2002;53:630-7

Uy et al. (Baylor)IMRT for meningiomaInt J Radiat Oncol Biol Phys 2002;53:1265-7

De Neve W et al.Lethal pneumonitis in a phase I study of chemotherapy And IMRT for lung cancerRadiother Oncol 2005

And a cautionary note…….

IMRT StudiesProspective cooperative group trials evaluating IMRT are now appearing

Most importantly, Phase III clinical trials are being undertaken

ASTRO Meeting 2006Philadelphia

“IMRT Era”Truly an exciting time for IMRTBecoming standard in many disease sitesAlso being used in ever more sophisticated ways

IMRT will becomeincreasingly commonin the treatmentrecurrent disease

Stephanie Milker-Zabel (Heidelberg)IMRT for Recurrent Spinal MetastasisIMRT: A Clinical Perspective BC Decker 2005

Electron IMRT

Isodose distribution ofa parotid cancer plannedwith electron IMRT

↑conformity and sparingof underlying tissues

Song Y, Boyer A, Xing L et al. (Stanford)Modulated Electron Radiation Therapy IMRT: A Clinical Perspective BC Decker 2005

“Repair” of Unacceptable Brachytherapy Prostate Implants

Li XA, Wang JZ (U Maryland)Repair of Unacceptable ImplantsIMRT: A Clinical Perspective BC Decker 2005

Original Brachy IMRT Brachy + IMRT

Replacement of BrachytherapyCervical Cancer

Low DA (Washington U)Applicator-Guided IMRTIMRT: A Clinical Perspective BC Decker 2005

HDR Applicator-GuidedIMRT

Accelerated Concomitant Boost IMRTBreast Cancer

Whole breast: 40.5 in 2.7 Gy fractions per day

Lumpectomy Site: 48 Gy in3.2 Gy fractions per day

Tot al time = 3 weeks (15 fx)

Eugene Lief, Silvia Formenti (NYU)Accelerated Concomitant Boost IMRTIMRT: A Clinical Perspective BC Decker 2005

Proton IMRT

Lomax AIntensity Modulated Proton TherapyIMRT: A Clinical Perspective BC Decker 2005

IM-proton plan ina 10 year old girl witha lumbar chordoma

Revolution Continues

IMRT

Image GuidedIMRTVarian Trilogy

But one must always remember to keep an eye on the ball

Key to Successful IMRTOptimal Target Delineation

The value and importance of conferences such as these will never diminish…..

Thank YouEnjoy the Conference