Radiotherapy

Presented by: Dr. Nikil Jain

contents

Introduction

The Basis of Radiotherapy

Radiation Techniques

Side effects of radiotherapy

Future Development in Radiotherapy

What is Radiotherapy

Use of ionising radiation to treat cancers

Source of ionising radiation : Natural : Uranium,

Plutonium, Radium Cobalt, Iodine, Gold, Iridium

Man made : LINAC, cyclotrons

Introduction1898 - Roentgen discovers x-rays1903 - Gruber treats Ca Breast with radiotherapy1950 - Cobalt teletherapy

- Gamma knife1970 - LINAC1990 - “Conformal RT techniques”

- Stereotactic Radiotherapy- 3D conformal RT- Inverse treatment planning- cyberknife, - intra-operative RT- chemo-RT- altered fractionation

Role of RT

50% of all Ca will require RT

2/3 of these for curative intent

Curative Role : Head and Neck Ca Ca Cervix Anal and skin Ca Prostate Ca Bladder Ca Early Lung Ca Early Ca Oesophagus Seminoma Hodgkin’s disease and NHL Medulloblastomas and some brain

tumours

How are x-rays produced?

Natural : radioactive decay

Man-made : sudden deceleration of high speed electrons when it hits a tungsten target

Biological Effects of RT

1. RT causes “ionization” in tissue

2. This forms “free radicals”

3. Free radicals - interact and damage DNA

4. During mitosis, abnormal DNA unable to

replicate, causing cell death

Cellular Effects of Radiation

Inhibition of specific biochemical processes in

cells (eg respiration, protein synthesis)

require very high doses (10-100Gy)

Chromosomal aberrations (1Gy)

Inhibition of reproductive ability :< 10Gy - divide a few times> 20Gy - lyse without entering mitosis

Interaction of RT and Matter Direct action

direct interaction with critical targets in cells

Indirect actionreacts with H20 to form free radicalfree radical highly reactivefree radicals diffuse to DNA- produce damage to DNA

biological effects results

Biological Effects of RT DNA strand breaks

Breaks in the chromosomes

results in - restitution (rejoin)

- aberration (fail to rejoin)

- rejoin other broken ends (give rise to gross

distortion)

Outcome of Radiation Damage

Cell survives

Cell dies - mitotic cell death

- intermitotic death

(lymphocytes, ova, salivary

gland cells)

Cell repairs - given time, energy and

nutrientsItself

Chromosome aberrations in human lymphocytes

Used as biomarkers of radiation exposure

Blood samples taken within days-weeks

Lymphocytes stimulated to divide and

incidence of dicentrics and rings is scored

Dose can be estimated by comparing with in-

vitro cultures exposed to known doses

repair Radiation results in : lethal damage - ie

irreversible sublethal damage - ie can be repaired unless 2nd dose of RT

repair - because of shoulder in cell survival curve

repopulation When RT administered, some cells die,

some cells repair or escape damage with time these cells will replicate and

replace or repopulate the dead cells if the rate of repopulation exceeds the rate of cell

death, then the tumour will grow despite treatment thus repopulation

good for normal tissue bad for tumour

fractionation Allows repair of normal tissue Allows repopulation of normal tissue

Allows re-oxygenation of tumour Allows re-assortment

But

Allows repair of tumour Allows proliferation of tumour

Treatment plan is based on

Staging of disease using TNM classification

age of patient

co-morbid conditions-MedicalDentalSpeechNutritionPsychosocialSocioeconomic

Treatment Options

Primary surgery

Adjuvant Radiotherapy

Concurrent Chemotherapy

OR Primary Radiotherapy

Concurrent Chemotherapy

Surgery for Salvage

+/-

+/-

+/-

+/-

No treatment

Palliation

Radiation therapy is indicated following surgery if:soft tissue margin positiveone or more lymph nodes exhibit

extracapsular invasionbone invasion presentmore than one lymph node positive in the

absence of extracapsular invasioncomorbid immunosuppressive disease

present, or perineural invasion occurre

Aims of radiation Deliver a precise dose of radiation to a

defined tumor volume with as minimal damage as possible to surrounding normal tissues

- Eradication of the tumor- Improvement of quality of life- Prolongation of survival

Terms used in Radiotherapy Gray is Radiation Absorption Dose in the

medium= RAD 1 Gy = 100 rads 1 cGy = 1 rad Field or portal = The name of the radiation

beam entering thro’ the anatomical site of body. Eg) Rt lateral, Lt lateral face portals

DIFFERENT TYPES OF RADIOTHERAPY External beam therapy Brachytherapy Combined external beam and interstitial

brachytherapy Modification of tumor hypoxia Modified radiation fractionation Combined chemotherapy/radiotherapy Combined modified radiation fractionation

and simultaneous chemotherapy Intensity modulated radiotherapy or IMRT

Process of radiation oncology Clinical evaluation- Pathology- Staging work up- Patterns of spread and failure Therapeutic decision:goal of therapy- Curative:definitive,neoadjuvant or adjuvant- Palliative Selection of therapeutic modalities- Integration with surgery(pre op or post op)- Integration with chemotherapy Periodic evaluation (during treatment) and follow-

up- Careful assessment of acute and late toxicity

Pt-Radiation Processing Decision made for Treatment Consent CT Simulation with markers From CT Scan CT cuts are exported to TPS In TPS ,target volume/ critical structures are

contoured by Oncologists Medical physicist plans for RT with TPS Once plan is ready- for approval by Oncologist Plan exported to workstation Treatment setup done Setup verification done thro Portal Vision Treatment delivered Documentation

Treatment Machines Tele Cobalt-60 Cobalt 60- Gamma rays Capital Investment less Useful in most Practical Situations. Easy Installation Few Staff required Maintenance/Repair Easy Medical Linac Electrically Driven Investment more Sharper Beams. Higher tissue penetration Technically Superior Can produce Electron beams ,used to treat Neck nodes.

Medical Linac Electrically Driven Investment more Sharper Beams. Higher tissue penetration Technically Superior Can produce Electron beams ,used to treat

Neck nodes.

Medical Linear Accelarator

Linac Treatment Options X- Rays : Simple Complex 3D Conformal IMRT Electrons : In Head & Neck for LN, any Skin Cancers,Recurrence

IMRTIMRT Intensity modulated radiotherapy

Advanced form of 3D - conformal radiotherapy

based on the use of optimised non uniform beam intensities

determined by computer-based optimisation techniques (Inverse planning)

Clinical Processing for IMRT

Aquaplast Face Mask

Intra Oral Cone therapy Localized radiation technique More suitable for anteriorly located lesions RT by Intra oral cones uses 250 KeV x rays or

Electron beams Indications same like Brachytherapy Used after Ext Beam RT

Interstitial Brachytherapy Depends upon volume of growth. May be single plane,double plane, volume

implants. 0.5 – 1.0 cm margin around the growth. Stainless steel needles or after loading

catheters used for this. LDR (Caesium ) or HDR (Iridium) isotope used

thro after loading catheter.

• How much?

• Where?

Radiation dosimetry

1 “rad” = 1 centiGray (cGy)

200 cGy per day 5 days per week 1000 cGy per week Total dose ranges from 6000 cGy – 7000 cGy

6 – 7 WEEKS of treatment

Dental Care and Radiation Dental care should be a comprehensive part Evaluation before RT For dental carries Teeth Extn before RT RT will be delayed for 2 weeks after Extn. Sound teeth or teeth in good repair need not

be sacrificed. Post RT dental Extn possible with antibiotic

coverage,but better avoided within short period

Treatment Recommendations Lip Cancers T1 N0 :Surgery or RT if commissural

involvement or poorly different. Cancers T2 N0 :Surgery or RT Post op RT if margin +ve ; node +ve T 3-4 N0: Surgery ? Cosmetic/Functional

Outcome Post op RT +/- Chemo if +ve margin; node

+ve Alternatively Concomitant Chemo+RT first

and Surgery for Salvage.

T 1-4 Any N :Surgery +/- Contra lateral ND Post Op Chemo RT as indicated Margin + ve ; Margin close Node(s) + ve ; Poorly Different.Cancers Lympho Vascular Space invasion

Treatment Recommendations Floor of mouth Cancers T1 N0 : Surgery or RT +/- Brachytherapy Post

op RT as indicated . T2 N0 ,T3N0(Resectable):Surgery Post op Chemo RT as indicated. T1-4 N+ :Surgery Post op Chemo RT as indicated Locally advanced –unresectable Chemoradiation first Surgery for salvage

Treatment Recommendations Oral Tongue Cancers T1 & Early T2 N0:Surgery or RT In both Neck Treatment is required Post op RT as indicated Large T2 N0: Surgery Post Op Chemo RT If inoperable -Definitive RT T3-4 N0 or T1-4 N+ :Surgery Post op Chemo RT Alternatively Chemo RT first Surgery for Salvage if any nodes or residual

primary disease.

Treatment recommendation buccal mucosa External beam therapy most commonly used

for T1 and T2 tumors

Larger T3 and operable T4 tumors are more approptietly treated with surgery and post operative RT.

Treatment modalities lower alveolar mucosaClose proximity to underlying mandible ,bone

invation occurs

T1 and T2 tumors most frequently treated with external beam therapy

Extensively advanced tumor with more extensive require surgery and postoperative radiotherapy to include prophylactic lymphnode iiradiation

Treatment modalitiesretromolar trigone T1 and T2 Tumors can be effectively treated

with external beam therapy

Important to include ant. border of ramus and ptrygoid fossa superiorly to skull base with elective irradiation to ipsilateral lymphnode drainage

More advanced tumor require surgery followed by radiotherapy

Post op rt

Advantages- Benefit of pathology,surgical findings Better staging,no need to over treat

Disadvantages Larger RT fields to cover surgical bed Poorer blood suply – RT less effective More late morbidity

Pre-op RT

Advantages -Downstage tumour, less multilating

surgery-Sterilise surgical margins-Remove RT damaged parts during surgery

Disadvantages- Clinical staging, therefore treat some unnecessary-What if tumour not sensitive to RT?-May increase surgical morbidity

What Happens To A Patient Undergoing RT

Acute sequale General- Weight loss - Nausea - Fatigue- Depression Extra-Oral Intra-Oral- Cutaneous burns mucositis- Alopecia erythema- Xeroderma ulceration

Side Effects of RT

Epidermal layers of skin, GIT - fast turnover Thus RT kills the epidermal layers as they go into

mitosis Lower layers insufficient time to repopulate Thus de-sloughing occurs :-

-skin : erythema, dry then moist desquamation “sun burn”

-mucosa : mucositis, oesophagitis, gastritis, colitis proctitis, cystitis

- marrow : pan-cytopaenia

Side effects of RT to head & neck Xerostomia

From day 1 - Pilocarpine 5-10mg tid - Saliva substitutes (oral balance) - Ethyol (amifostine)

Serous component of saliva affected most often

-Bicarbonate mouth rinses

Mucositis

direct mucosal (basal layer) damage secondary infectionTreatment

- good oral hygiene- anti-fungals- salt water rinses- pain killers, steroids- lidocaine- soft diet- avoid spices, smokes, spirits

Hypoalimentation

nutrition counselling enteral feeding appetite stimulants (Megace,

anabolic steroids)

Skin Reactions

Erythema Dry desquamation (peeling)

hydrocortisone 1%

Moist desquamation (dermis exposed and oozes serum) gentian violet paraminol cream healing within 2-4 weeks after RT

Sialadenitis 5% develop it within 12 hrs of

1st RT transient painless enlargement

of salivary gland usually disappears within a week

despite continuation of treatment

Skin reactions Sense of Taste-

Begins with in one week Recovers with in 1-3 months

Alopecia

Only in areas which are irradiated Begins during the 3rd week of RT

Late Effects Of RTXerostomia dependent on dose (>35Gy) to parotids

Teeth pathologic changes secondary to diminished

salivary flow radiation caries

Trismus fibrosis of muscles of mastication expecially if treated with Sx+RT

Late effects of RT Brain Necrosis – Demyellination with loss of focal areas of

white matter necrosis Time interval : 8 months to 2 years Symptoms : dizziness

- Impaired memory, headache,- Confusion, fits, personality change- 16% - no sign or symptoms

Treatment - steroids

Soft tissue and bone necrosis Due to avascular effect of RT

Bone itself tolerates high dose of RT well, so long as tissues overlying the bone remain intact and the bone is not subjected to excessive stress or trauma

After RT, extraction of nonrestorable teeth within high dose areas is to be avoided unless all other measures fail. Try root-canal therapy

RT caries in teeth outside the field of RT does not predispose to osteonecrosis since the bone at this point has not received high-dose RT

Management Small exposures - conservative

- patience (mths)

HBO - 30-60 divesof 2.4atm/90min/day/5day/week

Surgical resection

Cranial nerve Optic Nerve Neuropathy

8% at doses of 60-73Gy No effective treatment Steroids, HBO

Hypoglossal Nerve esp if large subdiagastric LN RT -> fibrosis, nerve entrapment RT+RND - less risk

Brachial Plexus occur 6-24 mths later rare at 2Gy/# associated with large dose/#

RT induced 2nd Malignancies 1st case in1902 - hand of RT technician

RT induced Mucosal CA

MDAH - 1163 patients (Radiology 1975)- no excess new SCC

UCLA - 2125 patients (IJROBP 1988)- no diff in risk of 2nd Ca

RTOG - NPC database (Cancer 1922)- cf age-matched grp

- less 2nd Ca after RT

Rt induced sarcoma Incidence (Hatfield; Philips; Seydel; Bataini) 1-2 cases per 1000, 5yr survivor

Assuming 1 per 500, 5yr survivorAnd overall 5 yr surv for RT is 40%

Most are : high grade sarcomas, advanced stage difficult to operate respond poorly to chemo and consequently poor prognosis

RT Induced Thyroid Ca

Latent period : 10-30 yrs

Low doses of RT (<20Gy)

Advances in rt techniques Altered Fractionation Regiments Balance between tumour & normal tissue :

repair, re-oxygenation, re-assortment, re-population

Accelerated Fractionation overcome tumour repopulation

Hyperfractionation reduce dose/fraction to reduce late side

effects and permit higher total doses to be given to tumour

Chemo-RT “Spatial co-operation”

eg ALL (CNS) ‘hypoxic’ drugs

Synergistic actions eg 5FU, DDP, Paclitaxel

Sequencing chemo and RT

Neo-adjuvant Concomitant Adjuvant

Most evidence suggest concomitant chemo-RT is sequence which will result in improved results

H&N, lung, esophagus, cervix

Improving oxygenation HBO Hypoxic cell sensitiser Erythropoeitin Carbogen (95%CO2, 5%O2) Nicotinamide

Angiogenesis Endothelial cell biology Vascular targetting

Ratioprotectors (Ethyol)

Improved technology Fusion of CT/MRI/PET images 3D conformal RT Inverse treatment planning Real time target localisation

Cyberknife BAT u/s system

“Tomotherapy” - like CT Scan

Charged particles Precise dose localisation possible

eg protons

high LET (less dependence on O2)eg neutrons

“stars” - causes disintegration of nucleuseg pions (-ve pi mesons)

Conclusion Early detection of lesions is critical to

allow conservative treatment and protect the patient’s quality of life.

Many avenues constantly under investigation, are available to treat oral cancers, with improved methods

A multidisciplinary team can help oral cancer patients deal with the aftermath of treatment.

references Text book for oral cancer by Jatin P. Shah

Text book of oral &maxillofacial surgery by Peter Ward Booth.

Text book of radiology white & ferrow

Thank you