Radiotherapy as a part of multidisciplinary approach

in the treatment of malignomas

Dr. Tatiana Hadjieva, MD, PhD, D sc

Professor , Head University Radiotherapy Clinic

Medical University Sofia

Radiotherapy tackles all hallmarks of cancer

Solimini et al. Cell 2007

Multidisciplinary approach = Multimodality treatment of

malignomas Classical treatment methods

Surgery Radiotherapy Chemotherapy = Drug therapy with

Cytostatics

Hormones

Target therapy drugs

Immunomodulators

Vaccines

RT, chemotherapy, target therapy

Prescribing Radiotherapy Management decision

RT combined with surgery

Preoperative RT Postoperative RT Intraoperative RT

RT combine with Chemotherapy Simultaneous Postponed In sandwich

Radiotherapy alone Combined RT- different RT methods

Intracavitary curietherapy Interstitial curietherapy Metabolic curietherapy

(+/-)

Recent development in cancer strategy

6

Prescribing Radiotherapy Define tumour target

Staging umor Node Metastasis System- prognostic factors

Tumour histopathological characteristics - prognostic factors determined tumour biology

Definition of the goal of RT : curative palliative

Patients status (Karnofski index)

Prescribing Radiotherapy

Anatomical and topographical planning of RT Optimal tumour volume

Staging Histological parameters Lymph node involvement Tumour and normal tissue anatomy and topometry

Large volume Small volume boost

Optimal dose probability of tumour control Tumour Radiosensitivity ( RS) Radiocurability -

more then 90% probability of tumour control

High RS tumours : haemoblasoses lymphomas, semonomas, disgerminomas Doses 40 Gy conventional fractionation

Moderately RS tumours : epithelial neoplasmas carcinomas SCC (G1-G3 Ca cutis, colli uteri, ORL; adenocarcinomas Doses 60-70 Gy

Radioresistant tumours: mesenhymomas - bone and soft tissue sarcomas, some epithelial blastomas (adenosquamous or mucoepidermoid type)

Optimal dose probability of tumour control

Doses for different tumour volumes- more then 90%

probability of tumour control

Lymphoma 30-40 Gy Carcinoma Palpable tumour ( T1-T4) 60-80

Gy. Surgical margins -microscopical

disease 10 6 cells 60-65 Gy, Sub-clinical disease in lymph

nodes or arround the tumour less than 106 cells45-50 Gy

Optimal dose probability of tumour control versus

normal tissue tolerance

Tolerance dose TD 5/5 no more than 5% severe complication rate within 5 years of treatment

Normal tissue tolerance dose depends: 1. Inrtnsic radiosensitivity of the tissue Normal tissue with low tolerance limiting dose tissue

haemopoetic tissue, reproductive organs, lens, spinal cord, liver, lung

Normal tissue with high tolerance non limiting dose tissues bones, muscles, nerves

2. Volume of the irradiated tissues 3. Fractionation - 4. Overall treatment time

Normal tissue tolerance Chronologically the manifestation depends on the kinetic property

of the tissue cells (slow or rapid renewal) and the dose given Early effects during and up to 3 months Late effects after 6 months No correlation between severity of acute and late effects- different cell

curves.

--- Early ef; Late ef

Dose volume histograme

heart

target volume

lungs

Immobilization and simulation

Immobilization CT simulation

3-D treatment planning Correlation of multi-serial CT scans for the tumour and the

normal surrounding tissue

doctor

Fussed FDG CT scans

Change in RT goal from radiacak palliative (Cadwell, I J Rad Oncol, Biol Phys, 2001 51, 923)

Dosimetry CT system for treatment planning anatomical and dosimetry moduls

Physisist

-

Dosimetry planing Optimisation of the radiation quality gamma

photons, X-ray photons, electrons

Basic techniques Two opposite fields Four- fields box

Multiple -fields Rotation

Conformal RT by Multilief collimator

28

Innovations

Application of radiotherapy Reproducibility and realization of treatment plan

Patients fixation and imobilisation

Control of dosimetry Verification systems -visualization of

RT portals

CT in treat room

Cone beam CT

Volumetric Modulated Arc Treatment

KV KV verification & matching

CBCT Imaging

Adaptive treatment

Tomotherapy Tumour shrinkage

Cyber knife Combination of low energy Linac with

movable arm moving arround the patient on the PC command\

Navigation recognize tumour and normal tissue image by imaging system

And adapts according the patient small movements

Short course fraction 1-5 The session is long 30 -70 minutes, patient

asleeps with music Wake up session has finished

180

70,000 ? 4; - 1; -

1; 1. -3; 3 ..

36

Exemple Ciber Knife

37

Optical nerve benign tumour Difficult for surgery.

Ciber Knife Lung cancer or metastates

100-180 fileds

38

Breast Cancer Radiotherapy Indications

Postoperative RT after breast preserving surgery in early BC Postoperative RT after mastectomy in advanced BC

RT in non operable BC

Palliative RT for BC

Postoperative RT after breast preserving surgery in early BC-

Is this necessary ??? Concept of whole breast IR

Cancer cells spreding in the periphery of major tumour (lland et al, Cancer, 1985

Radiotherapy in early breast cancer pTis, p1-2

Whole BR IR after lumpectomy

- long recurrence free survival

- good cosmesis

No RT after mastectomy in pT1pNoMo >=3 cm

-

National standard for breast cancer RT , 2002

Planning of RT for early BC

Radiotherapy techniques for early BC

Large volume : remaining breast and chest wall 50 Gy

Small volume boost overdosage 10-20 Gy; total dose 60-70 Gy

method -Marinova , 2000

IO boost

Survival curves in early breast cancer after quadrantectomie

Marinova 2000

.

,

0.890.900.910.920.930.940.950.960.970.980.991.001.011.021.031.041.05

0 2 4 6 8 10 12 14

n=341

COSMETIC RESULTS

Clinical visit Photos Schedules for

aesthetic evaluation: - Hyperpigmentation,

telangiectasias - Hypertrophic scar - Breast edema - Differences in profile - Differences in

consistency

Radiotherapy for advanced cancer Chemotherapy preceded RT

Why? The risk for tumour dissemination is more

dangerous than risk or loco-regional recurrence

Consolidation radiotherapy Positive lymph nodes with primary

tumour

N+ treatment in breast cancer

Electron-photon irradiation if int mammary chain is

involved

Palliative RT

Mono-bone Metastasis quality of life

dose regimes: one fraction of 8 Gy replaced 10 x 3 Gy; 4 5 Gy

Multiple Bone Mets Local analgetic RT Curietherapy 89 Sr, 32 Drug therapy diphosphonates, opiate

analgetics Brain mets palliative RT Lung Mets no RT

radiosensitiveness of the lung tissue

Radiotherapy for uterine

cervix

Indications for RT

Staging TNM = FIGO

combined brachy+EBRT

+RT

Carcinona in situ -TIS, or microinvasive cancer FIGO 0, I A

Only conisation

no RT

If absolute contraindications for surgery exist

RT is the alternative of surgery Intracavitary curietherapy (45-50 Gy in point A

(whole uterus)

FIGO IB - II A Radical hysterectomy + postoperative RT ( after 1964)

16-25% pelvic 2-11% paraaortic lymph metastases

Or Combine RT ( external beam RT and intracavitary curieterapy

Similar survival

Preference depends on the practice of the institution, patients age and tumour parameters.

National standard for cervix cancer RT , 2002

Postoperative Radiotherapy for operated FIGO IB- IIA

Planning volume pelvis and the superior third of the vagina

Doses: daily fraction of 2 Gy ; total dose 50Gy.

National standard for cervix cancer RT , 2002

3D conformal Irradiation

National standard for cervix cancer RT , 2002 Extended field irradiation for

high -risk patients (pelvic node positive )

Preoperative RT for FIGO IB- IIA-B

Indications

Bulky IB tumour

Primarily Inoperable tumour -II A-B

Total dose 30-40 Gy

?

National standard for cervix cancer RT , 2002

Preoperative RT effect on tumour MRI sagittal T2 image, 3D volume analysis

Preoperative RT 99 cm 3

After 22 Gy- 22 cm 3 - 78% reduction

Advanced cervix cancer FIGO IIB, III IV

Combine RT (external beam RT with intracavitary curieterapy )

National standard for cervix cancer RT , 2002

Advanced cervix cancer FIGO IIB, III IV

External beam RT for pelvic area (30-40 Gy),

Intracavitary curieterapy (40-50 Gy in point A to a total dose up to 70-80 Gy)

External beam RT for parametria up to 56-60 Gy.

External beam RT for paraortic nodes

National standard for cervix cancer RT , 2002

Uterus HDR Brachytherapy

HDR brachytherapy /

Definitive RT = Radiotherapy alone

If the patient remains inoperable after preoperative external beam irradiation, or/and there are no conditions for curietherapy the preoperative external beam irradiation continues as definitive RT.

If there is high-risk for paraortic metastases- irradiation of the area.

National standard for cervix cancer RT , 2002

Palliative RT FIGO IVB

Palliative external beam RT - symptoms Decompressive Analgetic Antihemorrhagic Bone mets metabolic curietherapy 32- , 89-Sr

Results

Radiotherapy for skin cancer

Curable disease epethelial tumours - carcinomas

Aggressive tumours malign melanomas

Treatment of carcinomas

Surgery Radiotherapy Radiotherapy- better function and cosmesis

Interstitial curietherapy > EBRT Radiotherapy > Surgery Deep adherent lesions, multiple lesions, lymph node metastases

Radiotherapy for cancer of the lips

Orthovoltage radioterapy - 60 keV Dose 60 Gy in different fractionation Curable disease

pT1-2- 100-90%

Brachytherapy - 50-70 Gy 5-7 days

External beam RT by electrons

Daily Fractions 2-5 Gy ,

6-20 fractions Total dose 50-60 Gy

Other indication for RT ENT region nasopharynx, larynx Abdominal Region rectal cancer,

endometrial cancer, testicular seminoma Hodgkin and Non- Hodgkin malignant

Lymphomas Benign disease main principles Degenerative diseases main principles

RT RTCH

Radiotherapy as a part of multidisciplinary approach in the treatment of malignomasRadiotherapy tackles all hallmarks of cancerMultidisciplinary approach = Multimodality treatment of malignomasRT, chemotherapy, target therapyPrescribing RadiotherapySlide Number 6Prescribing RadiotherapySlide Number 8 Prescribing Radiotherapy Anatomical and topographical planning of RTOptimal dose probability of tumour controlOptimal dose probability of tumour controlOptimal dose probability of tumour control versus normal tissue toleranceNormal tissue toleranceDose volume histogrameImmobilization and simulation 3-D treatment planningCorrelation of multi-serial CT scans for the tumour and the normal surrounding tissueSlide Number 18Slide Number 19Fussed FDG CT scansDosimetry CT system for treatment planning anatomical and dosimetry moduls - Slide Number 24Dosimetry planingBasic techniquesConformal RTby Multilief collimatorSlide Number 28Slide Number 29Application of radiotherapy Reproducibility and realization of treatment planControl of dosimetryVerification systems -visualization of RT portalsVolumetric Modulated Arc TreatmentKV KV verification & matchingCBCT ImagingAdaptive treatment Cyber knife Exemple Ciber KnifeCiber KnifeLung cancer or metastatesBreast Cancer Radiotherapy IndicationsPostoperative RT after breast preserving surgery in early BC- Is this necessary ???Concept of whole breast IRRadiotherapy in early breast cancer pTis, p1-2Planning of RT for early BCSlide Number 43Radiotherapy techniques for early BC Large volume : remaining breast and chest wall 50 GySmall volume boost overdosage 10-20 Gy; total dose 60-70 Gy method -Marinova , 2000IO boostSlide Number 47Survival curves in early breast cancer after quadrantectomie Marinova 2000COSMETIC RESULTSRadiotherapy for advanced cancerChemotherapy preceded RTWhy? The risk for tumour dissemination is more dangerous than risk or loco-regional recurrence N+ treatment in breast cancerElectron-photon irradiation if int mammary chain is involvedPalliative RTSlide Number 54Indications for RTSlide Number 56 Carcinona in situ -TIS, or microinvasive cancer FIGO 0, I A FIGO IB - II A Postoperative Radiotherapy for operated FIGO IB- IIA3D conformal IrradiationNational standard for cervix cancer RT , 2002 Extended field irradiation forhigh -risk patients(pelvic node positive ) Preoperative RT for FIGO IB- IIA-BPreoperative RT effect on tumourMRI sagittal T2 image, 3D volume analysisAdvanced cervix cancer FIGO IIB, III IV Advanced cervix cancer FIGO IIB, III IVSlide Number 66Uterus HDR BrachytherapyHDR brachytherapy /Definitive RT = Radiotherapy alonePalliative RT FIGO IVB ResultsRadiotherapy for skin cancerRadiotherapy for cancer of the lipsSlide Number 74External beam RT by electronsOther indication for RTSlide Number 77Slide Number 78